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A Study of Emicizumab Administered Subcutaneously (SC) in Pediatric Participants With Hemophilia A and Factor VIII (FVIII) Inhibitors (HAVEN 2)

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ClinicalTrials.gov Identifier: NCT02795767
Recruitment Status : Completed
First Posted : June 10, 2016
Results First Posted : April 10, 2019
Last Update Posted : June 2, 2021
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Intervention Drug: Emicizumab
Enrollment 88
Recruitment Details Following completion of accrual to Cohort A: 1.5 mg/kg Emicizumab QW, enrollment was opened to Cohort B: 3 mg/kg Emicizumab Q2W and Cohort C: 6 mg/kg Emicizumab Q4W. Of note, enrollment remained open to Cohort A only for participants who were <2 years old, and enrollment to Cohorts B and C was limited to participants who were 2-11 years old.
Pre-assignment Details  
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first. Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first. Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Period Title: Overall Study
Started 68 10 10
Received at Least One Dose of Emicizumab 68 10 10
Dose Up-Titrated to 3 mg/kg QW 0 0 3
Completed 52 Weeks in Study 67 10 9
Completed 67 10 10
Not Completed 1 0 0
Reason Not Completed
Received Commercial Emicizumab             1             0             0
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W Total
Hide Arm/Group Description Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first. Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first. Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first. Total of all reporting groups
Overall Number of Baseline Participants 68 10 10 88
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 68 participants 10 participants 10 participants 88 participants
6.2  (3.6) 6.9  (3.2) 7.9  (3.0) 6.5  (3.5)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 10 participants 10 participants 88 participants
0 to <2 Years Old
8
  11.8%
0
   0.0%
0
   0.0%
8
   9.1%
2 to <6 Years Old
19
  27.9%
3
  30.0%
2
  20.0%
24
  27.3%
6 to <12 Years Old
38
  55.9%
7
  70.0%
8
  80.0%
53
  60.2%
≥12 Years Old
3
   4.4%
0
   0.0%
0
   0.0%
3
   3.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 10 participants 10 participants 88 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
68
 100.0%
10
 100.0%
10
 100.0%
88
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 10 participants 10 participants 88 participants
Hispanic or Latino
5
   7.4%
1
  10.0%
1
  10.0%
7
   8.0%
Not Hispanic or Latino
61
  89.7%
9
  90.0%
9
  90.0%
79
  89.8%
Unknown or Not Reported
2
   2.9%
0
   0.0%
0
   0.0%
2
   2.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 10 participants 10 participants 88 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
10
  14.7%
1
  10.0%
2
  20.0%
13
  14.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
11
  16.2%
1
  10.0%
0
   0.0%
12
  13.6%
White
39
  57.4%
7
  70.0%
8
  80.0%
54
  61.4%
More than one race
2
   2.9%
0
   0.0%
0
   0.0%
2
   2.3%
Unknown or Not Reported
6
   8.8%
1
  10.0%
0
   0.0%
7
   8.0%
Number of Participants with 0, 1, or >1 Target Joint in the Last 24 Weeks Prior to Study Entry   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 10 participants 10 participants 88 participants
0 Target Joints
44
  64.7%
3
  30.0%
7
  70.0%
54
  61.4%
1 Target Joint
9
  13.2%
6
  60.0%
1
  10.0%
16
  18.2%
>1 Target Joint
15
  22.1%
1
  10.0%
2
  20.0%
18
  20.5%
[1]
Measure Description: A target joint was defined as a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.
1.Primary Outcome
Title Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
0.3
(0.17 to 0.50)
2.Primary Outcome
Title Cohort A: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Hide Description The number of all bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: all bleed rate per year
3.2
(1.94 to 5.22)
3.Primary Outcome
Title Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated spontaneous bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated spontaneous bleed rate per year
0.0
(0.0 to 0.1)
4.Primary Outcome
Title Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated joint bleed rate per year
0.2
(0.08 to 0.29)
5.Primary Outcome
Title Cohort A: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated target joint bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated target joint bleed rate per year
NA [1] 
(NA to NA)
[1]
The model-based ABR and 95% CI were not estimable because too few events had occurred over the efficacy period to calculate values using the negative binomial regression model; 95.4% of participants in this cohort had 0 treated target joint bleeds.
6.Primary Outcome
Title Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Mean (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
0.3
(0.00 to 4.31)
7.Primary Outcome
Title Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Hide Description The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Mean (95% Confidence Interval)
Unit of Measure: all bleed rate per year
3.2
(0.70 to 9.04)
8.Primary Outcome
Title Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Mean (95% Confidence Interval)
Unit of Measure: treated spontaneous bleed rate per year
0.0
(0.00 to 3.74)
9.Primary Outcome
Title Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Mean (95% Confidence Interval)
Unit of Measure: treated joint bleed rate per year
0.2
(0.00 to 4.01)
10.Primary Outcome
Title Cohort A: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Mean (95% Confidence Interval)
Unit of Measure: treated target joint bleed rate per year
0.1
(0.00 to 3.84)
11.Primary Outcome
Title Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Median (Inter-Quartile Range)
Unit of Measure: treated bleed rate per year
0.0
(0.00 to 0.00)
12.Primary Outcome
Title Cohort A: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Hide Description The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Median (Inter-Quartile Range)
Unit of Measure: all bleed rate per year
0.6
(0.00 to 2.92)
13.Primary Outcome
Title Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Median (Inter-Quartile Range)
Unit of Measure: treated spontaneous bleed rate per year
0.0
(0.00 to 0.00)
14.Primary Outcome
Title Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Median (Inter-Quartile Range)
Unit of Measure: treated joint bleed rate per year
0.0
(0.00 to 0.00)
15.Primary Outcome
Title Cohort A: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Median (Inter-Quartile Range)
Unit of Measure: treated target joint bleed rate per year
0.0
(0.00 to 0.00)
16.Primary Outcome
Title Cohort A: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
76.9
(64.8 to 86.5)
0-3 Bleeds
100.0
(94.5 to 100.0)
0-10 Bleeds
100.0
(94.5 to 100.0)
>10 Bleeds
0.0
(0.0 to 5.5)
17.Primary Outcome
Title Cohort A: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
49.2
(36.6 to 61.9)
0-3 Bleeds
72.3
(59.8 to 82.7)
0-10 Bleeds
92.3
(83.0 to 97.5)
>10 Bleeds
7.7
(2.5 to 17.0)
18.Primary Outcome
Title Cohort A: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
96.9
(89.3 to 99.6)
0-3 Bleeds
100.0
(94.5 to 100.0)
0-10 Bleeds
100.0
(94.5 to 100.0)
>10 Bleeds
0.0
(0.0 to 5.5)
19.Primary Outcome
Title Cohort A: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
84.6
(73.5 to 92.4)
0-3 Bleeds
100.0
(94.5 to 100.0)
0-10 Bleeds
100.0
(94.5 to 100.0)
>10 Bleeds
0.0
(0.0 to 5.5)
20.Primary Outcome
Title Cohort A: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks; At the primary completion date, the median (min-max) duration of the efficacy period in Cohort A was 57.57 (17.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohort A who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
95.4
(87.1 to 99.0)
0-3 Bleeds
100.0
(94.5 to 100.0)
0-10 Bleeds
100.0
(94.5 to 100.0)
>10 Bleeds
0.0
(0.0 to 5.5)
21.Secondary Outcome
Title Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
0.2
(0.03 to 1.72)
2.2
(0.69 to 6.81)
22.Secondary Outcome
Title Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Hide Description The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: all bleed rate per year
1.5
(0.62 to 3.40)
3.8
(1.42 to 10.11)
23.Secondary Outcome
Title Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated spontaneous bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated spontaneous bleed rate per year
NA [1] 
(NA to NA)
0.8
(0.05 to 12.00)
[1]
The model-based ABR and 95% CI were not estimable because too few events had occurred over the efficacy period to calculate values using the negative binomial regression model; 100% of participants in this cohort had 0 treated spontaneous bleeds.
24.Secondary Outcome
Title Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated joint bleed rate per year
0.2
(0.03 to 1.72)
1.7
(0.60 to 4.89)
25.Secondary Outcome
Title Cohorts B and C: Model-Based Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated target joint bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated target joint bleed rate per year
0.2
(0.03 to 1.72)
0.5
(0.05 to 5.88)
26.Secondary Outcome
Title Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
0.2
(0.00 to 4.13)
2.5
(0.43 to 8.06)
27.Secondary Outcome
Title Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Hide Description The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: all bleed rate per year
1.5
(0.10 to 6.36)
4.0
(1.09 to 10.25)
28.Secondary Outcome
Title Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: treated spontaneous bleed rate per year
0.0 [1] 
(NA to 3.69)
0.8
(0.01 to 5.20)
[1]
The lower limit of the 95% CI could not be estimated because too few events had occurred over the efficacy period to calculate it; 100% of participants in this cohort had 0 treated spontaneous bleeds.
29.Secondary Outcome
Title Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: treated joint bleed rate per year
0.2
(0.00 to 4.13)
1.9
(0.23 to 7.14)
30.Secondary Outcome
Title Cohorts B and C: Mean Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: treated target joint bleed rate per year
0.2
(0.00 to 4.13)
0.5
(0.00 to 4.72)
31.Secondary Outcome
Title Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Median (Inter-Quartile Range)
Unit of Measure: treated bleed rate per year
0.0
(0.00 to 0.00)
0.0
(0.00 to 3.26)
32.Secondary Outcome
Title Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants <12 Years of Age
Hide Description The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Median (Inter-Quartile Range)
Unit of Measure: all bleed rate per year
0.0
(0.00 to 2.81)
1.6
(0.00 to 4.84)
33.Secondary Outcome
Title Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Spontaneous Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Median (Inter-Quartile Range)
Unit of Measure: treated spontaneous bleed rate per year
0.0
(0.00 to 0.00)
0.0
(0.00 to 0.00)
34.Secondary Outcome
Title Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Median (Inter-Quartile Range)
Unit of Measure: treated joint bleed rate per year
0.0
(0.00 to 0.00)
0.0
(0.00 to 3.26)
35.Secondary Outcome
Title Cohorts B and C: Median Calculated Annualized Bleed Rate (ABR) for Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Median (Inter-Quartile Range)
Unit of Measure: treated target joint bleed rate per year
0.0
(0.00 to 0.00)
0.0
(0.00 to 0.00)
36.Secondary Outcome
Title Cohorts B and C: Percentage of Participants by Categorized Number of Treated Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated bleeds over the efficacy period is presented here. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
90.0
(55.5 to 99.7)
60.0
(26.2 to 87.8)
0-3 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
0-10 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
>10 Bleeds
0.0
(0.0 to 30.8)
0.0
(0.0 to 30.8)
37.Secondary Outcome
Title Cohorts B and C: Percentage of Participants by Categorized Number of All Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of all bleeds over the efficacy period is presented here. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
60.0
(26.2 to 87.8)
50.0
(18.7 to 81.3)
0-3 Bleeds
100.0
(69.2 to 100.0)
90.0
(55.5 to 99.7)
0-10 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
>10 Bleeds
0.0
(0.0 to 30.8)
0.0
(0.0 to 30.8)
38.Secondary Outcome
Title Cohorts B and C: Percentage of Participants by Categorized Number of Treated Spontaneous Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated spontaneous bleeds over the efficacy period is presented here. A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
100.0
(69.2 to 100.0)
90.0
(55.5 to 99.7)
0-3 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
0-10 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
>10 Bleeds
0.0
(0.0 to 30.8)
0.0
(0.0 to 30.8)
39.Secondary Outcome
Title Cohorts B and C: Percentage of Participants by Categorized Number of Treated Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated joint bleeds over the efficacy period is presented here. A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Only treated bleeds that fulfilled the 72-hour rule were included in the analysis of treated joint bleeds, excluding bleeds due to surgery/procedure.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
90.0
(55.5 to 99.7)
60.0
(26.2 to 87.8)
0-3 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
0-10 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
>10 Bleeds
0.0
(0.0 to 30.8)
0.0
(0.0 to 30.8)
40.Secondary Outcome
Title Cohorts B and C: Percentage of Participants by Categorized Number of Treated Target Joint Bleeds Over the Efficacy Period in Treated Participants <12 Years of Age
Hide Description The percentage of participants by categorized number of treated target joint bleeds over the efficacy period is presented here. A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 24 weeks; At the primary completion date, the median (min-max) duration of the efficacy periods in Cohorts B and C were 21.29 (18.6-24.1) weeks and 19.86 (8.9-24.1) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts B and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
90.0
(55.5 to 99.7)
90.0
(55.5 to 99.7)
0-3 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
0-10 Bleeds
100.0
(69.2 to 100.0)
100.0
(69.2 to 100.0)
>10 Bleeds
0.0
(0.0 to 30.8)
0.0
(0.0 to 30.8)
41.Secondary Outcome
Title Cohort A: Intra-Participant Comparison of the Model-Based ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the Non-Interventional Study (NIS) Population
Hide Description This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for treated bleeds (i.e., number of treated bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study
Arm/Group Title Cohort A NIS Population (<12 Years): Bypassing Agents Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).
Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 18 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
19.9
(15.33 to 25.85)
0.2
(0.11 to 0.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort A NIS Population (<12 Years): Bypassing Agents, Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
0.006 to 0.023
Estimation Comments Emicizumab QW is the numerator and Prophylactic/Episodic Bypassing Agent is the denominator.
42.Secondary Outcome
Title Cohort A: Intra-Participant Comparison of the Model-Based ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Hide Description This is an intra-participant comparison of the model-based annualized bleeding rate (ABR) for all bleeds (i.e., number of all bleeds over efficacy period using negative binomial regression model) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study
Arm/Group Title Cohort A NIS Population (<12 Years): Bypassing Agents Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).
Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 18 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: all bleed rate per year
31.9
(22.68 to 44.81)
3.3
(1.45 to 7.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort A NIS Population (<12 Years): Bypassing Agents, Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.051 to 0.210
Estimation Comments Emicizumab QW is the numerator and Prophylactic/Episodic Bypassing Agent is the denominator.
43.Secondary Outcome
Title Cohort A: Intra-Participant Comparison of the Median Calculated ABR for Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Hide Description This is an intra-participant comparison of the calculated ABR for treated bleeds (annualized per participant using the following formula: ABR = [number of bleeds/number of days during the efficacy period] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study
Arm/Group Title Cohort A NIS Population (<12 Years): Bypassing Agents Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).
Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 18 18
Median (Inter-Quartile Range)
Unit of Measure: treated bleed rate per year
16.2
(11.49 to 25.78)
0.0
(0.00 to 0.56)
44.Secondary Outcome
Title Cohort A: Intra-Participant Comparison of the Median Calculated ABR for All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Hide Description This is an intra-participant comparison of the calculated annualized bleeding rate (ABR) for all bleeds (annualized for each participant using the following formula: ABR = [number of bleeds/number of days during the efficacy period] x 365.25) on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study
Arm/Group Title Cohort A NIS Population (<12 Years): Bypassing Agents Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).
Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 18 18
Median (Inter-Quartile Range)
Unit of Measure: all bleed rate per year
21.3
(14.18 to 44.47)
1.1
(0.00 to 2.30)
45.Secondary Outcome
Title Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of Treated Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Hide Description This is an intra-participant comparison of the percentage of participants by categorized number of treated bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). A "treated bleed" is a bleed directly followed by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and first treatment thereafter are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study
Arm/Group Title Cohort A NIS Population (<12 Years): Bypassing Agents Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).
Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 18 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
5.6
(0.1 to 27.3)
72.2
(46.5 to 90.3)
0-3 Bleeds
16.7
(3.6 to 41.4)
100.0
(81.5 to 100.0)
0-10 Bleeds
66.7
(41.0 to 86.7)
100.0
(81.5 to 100.0)
>10 Bleeds
33.3
(13.3 to 59.0)
0.0
(0.0 to 18.5)
46.Secondary Outcome
Title Cohort A: Intra-Participant Comparison of Percentage of Participants by Categorized Number of All Bleeds on Study Versus Pre-Study in Treated Participants <12 Years of Age From the NIS Population
Hide Description This is an intra-participant comparison of the percentage of participants by categorized number of all bleeds over the efficacy period on study versus pre-study in the NIS population who had previously participated in study BH29768 (NCT02476942). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame Up to 24 weeks in NIS BH29768 (NCT02476942) prior to study entry and from Baseline to 52 weeks on this study; At primary completion date, the median (min-max) duration of the efficacy period in the NIS population was 88.57 (55.9-92.6) weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants <12 years of age who had participated in NIS BH29768 (NCT02476942) prior to enrollment in this study and were on the same dose of emicizumab for at least 12 weeks in this study
Arm/Group Title Cohort A NIS Population (<12 Years): Bypassing Agents Cohort A NIS Population (<12 Years): 1.5 mg/kg Emicizumab QW
Hide Arm/Group Description:
This group includes historical data from participants <12 years old who had participated in the non-interventional study (NIS) BH29768 (NCT02476942) in which they had received prophylactic or episodic treatment with bypassing agents and had been followed for a minimum of 24 weeks on the NIS prior to enrollment in Cohort A of this study (BH29992).
Participants <12 years old who had previously received prophylactic or episodic treatment with bypassing agents in NIS BH29768 (NCT02476942) and were enrolled in Cohort A of this study (BH29992) received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 18 18
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0 Bleeds
0.0
(0.0 to 18.5)
33.3
(13.3 to 59.0)
0-3 Bleeds
11.1
(1.4 to 34.7)
72.2
(46.5 to 90.3)
0-10 Bleeds
44.4
(21.5 to 69.2)
83.3
(58.6 to 96.4)
>10 Bleeds
55.6
(30.8 to 78.5)
16.7
(3.6 to 41.4)
47.Secondary Outcome
Title Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Hide Description The number of treated bleeds over the efficacy period is presented here as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 3 0 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
0.8
(0.25 to 2.40)
48.Secondary Outcome
Title Model-Based Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Hide Description The number of all bleeds over the efficacy period is presented as a model-based ABR that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in followup times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 3 0 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: all bleed rate per year
1.4
(0.49 to 4.16)
49.Secondary Outcome
Title Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Hide Description The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 3 0 0
Median (Inter-Quartile Range)
Unit of Measure: treated bleed rate per year
0.9
(0.00 to 1.14)
50.Secondary Outcome
Title Median Calculated Annualized Bleed Rate (ABR) for All Bleeds in Treated Participants ≥12 Years of Age and <40 kg Body Weight
Hide Description The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab and were ≥12 years old and weighed <40 kg at the time of informed consent; none of the participants enrolled in Cohorts B and C fit these criteria.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 3 0 0
Median (Inter-Quartile Range)
Unit of Measure: all bleed rate per year
0.9
(0.00 to 2.84)
51.Secondary Outcome
Title Number of Treated Bleeds Over Time in Participants With Dose Up-Titration
Hide Description The number of treated bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to study completion (up to at least 52 weeks)
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Hide Analysis Population Description
All participants with emicizumab dose up-titration; At study completion, 0 participants in Cohorts A and B and 3 participants in Cohort C had their emicizumab dose up-titrated over the course of this clinical trial. Data were not aggregated for this outcome measure because it was not part of the pre-specified analysis plan and because of the limited sample size. The results will not be disclosed on an individual patient level because of data privacy concerns.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
52.Secondary Outcome
Title Number of All Bleeds Over Time in Participants With Dose Up-Titration
Hide Description The number of all bleeds over time was to be analyzed in participants whose emicizumab maintenance dose was up-titrated to 3 mg/kg QW if they had experienced suboptimal bleeding control on emicizumab at steady-state, per protocol criteria. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
Time Frame From Baseline to study completion (up to at least 52 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with emicizumab dose up-titration; At study completion, 0 participants in Cohorts A and B and 3 participants in Cohort C had their emicizumab dose up-titrated over the course of this clinical trial. Data were not aggregated for this outcome measure because it was not part of the pre-specified analysis plan and because of the limited sample size. The results will not be disclosed on an individual patient level because of data privacy concerns.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
53.Secondary Outcome
Title Long-Term Efficacy of Emicizumab in All Cohorts: Model-Based Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of bleeds over the efficacy period was shown as a model-based ABR that used a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed occurring in a joint. A "target joint bleed" is defined as a joint bleed in a target joint (≥3 bleeds have occurred over the last 24 weeks prior to study entry).
Time Frame From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65 10 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: bleed rate per year
Treated Bleeds
0.3
(0.19 to 0.43)
0.2
(0.06 to 0.54)
1.8
(0.32 to 10.59)
All Bleeds
3.0
(1.93 to 4.55)
0.8
(0.42 to 1.54)
2.4
(0.78 to 7.51)
Treated Spontaneous Bleeds
0.01
(0.01 to 0.07)
NA [1] 
(NA to NA)
0.9
(0.08 to 9.93)
Treated Joint Bleeds
0.2
(0.09 to 0.25)
0.2
(0.06 to 0.54)
1.3
(0.25 to 7.11)
Treated Target Joint Bleeds
0.1
(0.01 to 0.30)
0.1
(0.03 to 0.47)
0.5
(0.02 to 13.77)
[1]
The model-based ABR and 95% CI were not estimable because too few events had occurred over the efficacy period to calculate values using the negative binomial regression model; 100% of participants in this cohort had 0 treated spontaneous bleeds.
54.Secondary Outcome
Title Long-Term Efficacy of Emicizumab in All Cohorts: Mean Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.
Time Frame From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65 10 10
Mean (95% Confidence Interval)
Unit of Measure: bleed rate per year
Treated Bleeds
0.3
(0.00 to 4.25)
0.2
(0.00 to 4.02)
2.2
(0.32 to 7.59)
All Bleeds
3.0
(0.61 to 8.74)
0.8
(0.01 to 5.17)
3.0
(0.63 to 8.82)
Treated Spontaneous Bleeds
0.0
(0.00 to 3.72)
0.0 [1] 
(NA to 3.69)
1.0
(0.02 to 5.53)
Treated Joint Bleeds
0.1
(0.00 to 3.99)
0.2
(0.00 to 4.02)
1.6
(0.14 to 6.65)
Treated Target Joint Bleeds
0.1
(0.00 to 3.82)
0.1
(0.00 to 3.86)
0.5
(0.00 to 4.65)
[1]
The lower limit of the 95% CI could not be estimated because too few events had occurred over the efficacy period to calculate it; 100% of participants in this cohort had 0 treated spontaneous bleeds.
55.Secondary Outcome
Title Long-Term Efficacy of Emicizumab in All Cohorts: Median Calculated Annualized Bleed Rate (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds in Treated Participants <12 Years of Age
Hide Description The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. "All bleeds" included bleeds irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. Bleeds are classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "joint bleed" is defined as a bleed with type reported as "joint". A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.
Time Frame From Baseline to study completion (median [min-max] duration of the efficacy periods in Cohorts A, B, and C were 92.29 [36.1-187.7] weeks, 68.21 [56.7-129.4] weeks, and 69.43 [8.9-144.3] weeks, respectively)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Cohorts A, B, and C who were on the same dose of emicizumab for at least 12 weeks and were <12 years of age
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65 10 10
Median (Inter-Quartile Range)
Unit of Measure: bleed rate per year
Treated Bleeds
0.0
(0.00 to 0.51)
0.0
(0.00 to 0.40)
0.0
(0.00 to 3.26)
All Bleeds
0.7
(0.00 to 3.11)
0.8
(0.00 to 0.85)
0.6
(0.00 to 3.26)
Treated Spontaneous Bleeds
0.0
(0.00 to 0.00)
0.0
(0.00 to 0.00)
0.0
(0.00 to 0.00)
Treated Joint Bleeds
0.0
(0.00 to 0.00)
0.0
(0.00 to 0.40)
0.0
(0.00 to 3.26)
Treated Target Joint Bleeds
0.0
(0.00 to 0.00)
0.0
(0.00 to 0.00)
0.0
(0.00 to 0.00)
56.Secondary Outcome
Title Change From Baseline Over Time in the Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score, as Completed by Treated Participants ≥8 to <12 Years of Age
Hide Description The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and ranges from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
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Hide Analysis Population Description
All treated participants ≥8 to <12 years of age; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 22 6 6
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Baseline (value at visit) Number Analyzed 18 participants 6 participants 6 participants
33.37
(25.15 to 41.60)
25.60
(18.29 to 32.90)
25.12
(9.85 to 40.39)
Change from Baseline at Week 13 Number Analyzed 18 participants 6 participants 5 participants
-7.02
(-12.08 to -1.96)
-9.17
(-15.59 to -2.75)
0.29
(-23.12 to 23.69)
Change from Baseline at Week 25 Number Analyzed 18 participants 6 participants 4 participants
-9.17
(-15.97 to -2.37)
-13.21
(-23.43 to -2.99)
-14.64
(-42.98 to 13.70)
Change from Baseline at Week 37 Number Analyzed 17 participants 6 participants 3 participants
-11.64
(-16.11 to -7.17)
-15.48
(-24.58 to -6.37)
-17.86
(-71.56 to 35.85)
Change from Baseline at Week 49 Number Analyzed 17 participants 5 participants 3 participants
-9.62
(-13.59 to -5.65)
-15.14
(-25.05 to -5.24)
-16.43
(-67.33 to 34.47)
Change from Baseline at Week 57 Number Analyzed 12 participants 4 participants 2 participants
-11.13
(-17.92 to -4.34)
-16.43
(-25.85 to -7.01)
-25.00
(-215.59 to 165.59)
Change from Baseline at Week 81 Number Analyzed 12 participants 3 participants 0 participants
-11.79
(-20.23 to -3.34)
-14.52
(-31.76 to 2.71)
Change from Baseline at Week 105 Number Analyzed 9 participants 3 participants 0 participants
-18.57
(-35.25 to -1.90)
-14.76
(-30.76 to 1.24)
Change from Baseline at Week 129 Number Analyzed 7 participants 0 participants 0 participants
-14.90
(-29.47 to -0.32)
Change from Baseline at Week 153 Number Analyzed 4 participants 0 participants 0 participants
-14.46
(-32.37 to 3.44)
Change from Baseline at Week 177 Number Analyzed 2 participants 0 participants 0 participants
-5.36
(-118.81 to 108.09)
Change from Baseline at SC or ED Number Analyzed 11 participants 3 participants 2 participants
-13.05
(-22.31 to -3.79)
-21.43
(-37.40 to -5.46)
-28.21
(-241.50 to 185.07)
57.Secondary Outcome
Title Change From Baseline Over Time in the Haemo-QoL-SF Questionnaire Physical Health Domain Score, as Completed by Treated Participants ≥8 to <12 Years of Age
Hide Description The Haemo-QoL-SF is a self-reported questionnaire for children ≥8 years of age. It contains 35 items, which cover nine domains considered relevant for the children's health-related quality of life: Physical Health, Feelings, View of Yourself, Family, Friends, Other People, Sports and School, Dealing with Hemophilia, and Treatment. The Physical Health domain assesses hemophilia-related symptoms (painful swellings and presence of joint pain) and physical functioning (pain with movement). Items are rated with five respective response options: never, seldom, sometimes, often, and always. The Physical Health domain score ranges from 0 to 100, with a lower score reflective of better physical health.
Time Frame Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants ≥8 to <12 years of age; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 22 6 6
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (value at visit) Number Analyzed 18 participants 6 participants 6 participants
29.51
(16.38 to 42.65)
30.21
(21.49 to 38.93)
19.79
(-7.23 to 46.81)
Change from Baseline at Week 13 Number Analyzed 18 participants 6 participants 5 participants
-18.40
(-31.08 to -5.72)
-23.96
(-28.90 to -19.02)
3.75
(-46.12 to 53.62)
Change from Baseline at Week 25 Number Analyzed 18 participants 6 participants 4 participants
-18.40
(-33.76 to -3.05)
-17.71
(-26.43 to -8.99)
-17.19
(-61.94 to 27.57)
Change from Baseline at Week 37 Number Analyzed 17 participants 6 participants 3 participants
-21.32
(-36.61 to -6.04)
-25.00
(-33.30 to -16.70)
-22.92
(-85.66 to 39.83)
Change from Baseline at Week 49 Number Analyzed 17 participants 5 participants 3 participants
-15.44
(-25.74 to -5.15)
-23.75
(-40.57 to -6.93)
-25.00
(-96.15 to 46.15)
Change from Baseline at Week 57 Number Analyzed 12 participants 4 participants 2 participants
-17.19
(-29.99 to -4.39)
-23.44
(-32.96 to -13.92)
-25.00
(-342.66 to 292.66)
Change from Baseline at Week 81 Number Analyzed 12 participants 3 participants 0 participants
-14.06
(-26.97 to -1.15)
-16.67
(-25.63 to -7.70)
Change from Baseline at Week 105 Number Analyzed 9 participants 3 participants 0 participants
-16.67
(-45.29 to 11.96)
-20.83
(-29.80 to -11.87)
Change from Baseline at Week 129 Number Analyzed 7 participants 0 participants 0 participants
-12.50
(-45.71 to 20.71)
Change from Baseline at Week 153 Number Analyzed 4 participants 0 participants 0 participants
-21.88
(-66.72 to 22.97)
Change from Baseline at Week 177 Number Analyzed 2 participants 0 participants 0 participants
6.25
(-152.58 to 165.08)
Change from Baseline at SC or ED Number Analyzed 11 participants 3 participants 2 participants
-23.30
(-43.35 to -3.24)
-29.17
(-52.88 to -5.45)
-40.63
(-318.57 to 237.32)
58.Secondary Outcome
Title Change From Baseline Over Time in Caregiver-Reported Adapted Health-Related Quality of Life for Hemophilia Patients With Inhibitors Including Aspects of Caregiver Burden (Adapted Inhib-QoL) Questionnaire Total Score, Treated Participants <12 Years of Age
Hide Description Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. The Total Score is derived from the individual scores of all of the domains and it ranges from 0 to 100, with lower scores reflective of better HRQoL.
Time Frame Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants <12 years of age, as completed by their caregivers; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65 10 10
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (value at visit) Number Analyzed 58 participants 10 participants 10 participants
43.10
(39.63 to 46.56)
40.56
(32.46 to 48.65)
31.45
(19.93 to 42.97)
Change from Baseline at Week 13 Number Analyzed 58 participants 10 participants 9 participants
-19.76
(-23.55 to -15.96)
-21.46
(-27.21 to -15.72)
-9.24
(-21.69 to 3.21)
Change from Baseline at Week 25 Number Analyzed 58 participants 10 participants 8 participants
-21.67
(-25.39 to -17.94)
-26.11
(-32.64 to -19.58)
-13.93
(-24.21 to -3.64)
Change from Baseline at Week 37 Number Analyzed 57 participants 10 participants 7 participants
-21.79
(-25.30 to -18.28)
-24.62
(-32.28 to -16.97)
-12.55
(-25.73 to 0.64)
Change from Baseline at Week 49 Number Analyzed 56 participants 9 participants 7 participants
-22.12
(-25.50 to -18.74)
-24.57
(-32.66 to -16.49)
-18.18
(-31.98 to -4.38)
Change from Baseline at Week 57 Number Analyzed 41 participants 7 participants 6 participants
-20.86
(-24.87 to -16.85)
-24.37
(-34.52 to -14.22)
-20.28
(-39.65 to -0.92)
Change from Baseline at Week 81 Number Analyzed 32 participants 4 participants 4 participants
-22.29
(-27.58 to -17.00)
-24.95
(-35.71 to -14.18)
-14.84
(-33.45 to 3.76)
Change from Baseline at Week 105 Number Analyzed 20 participants 4 participants 4 participants
-18.04
(-26.73 to -9.34)
-21.82
(-43.00 to -0.64)
-15.82
(-31.09 to -0.55)
Change from Baseline at Week 129 Number Analyzed 16 participants 0 participants 0 participants
-15.43
(-24.41 to -6.46)
Change from Baseline at Week 153 Number Analyzed 7 participants 0 participants 0 participants
-11.68
(-29.51 to 6.14)
Change from Baseline at Week 177 Number Analyzed 6 participants 0 participants 0 participants
-22.41
(-42.41 to -2.40)
Change from Baseline at SC or ED Number Analyzed 52 participants 6 participants 4 participants
-23.59
(-27.38 to -19.80)
-25.83
(-36.77 to -14.89)
-13.73
(-52.15 to 24.69)
59.Secondary Outcome
Title Change From Baseline Over Time in the Caregiver-Reported Adapted Inhib-QoL Questionnaire Physical Health Domain Score, Treated Participants <12 Years of Age
Hide Description Proxy assessment of health-related quality of life (HRQoL) and aspects of caregiver burden were assessed using the Adapted Inhib-QoL questionnaire, which comprises two parts with a total of 30 questions. The first part asks the caregiver for his/her opinion on the child's HRQoL (proxy HRQoL) and consists of two scales: Physical Health and Treatment. The second part asks the caregiver to rate how the child's situation is for them (i.e., the impact of the child's disease and treatment on the caregiver) and consists of 6 scales (5 if the child does not have siblings): General Condition, Dealing with the Inhibitor, Perceive Treatment, Family Life, Siblings, Contact with Others. Items are rated with five respective response options: never, seldom, sometimes, often, and all the time. A total score is calculated as the sum of all of the items in the scale. The Physical Health domain score ranges from 0 to 100, with lower scores reflective of better physical health.
Time Frame Baseline (Week 1), Weeks 13, 25, 37, 49, 57, 81, 105, 129, 153, and 177, and at study completion [SC] or early discontinuation [ED] (up to 188 weeks)
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Hide Analysis Population Description
All treated participants <12 years of age, as completed by their caregivers; at each timepoint, the number analyzed is the number of participants who completed a sufficient number of questionnaire items.
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 65 10 10
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline (value at visit) Number Analyzed 58 participants 10 participants 10 participants
37.13
(31.69 to 42.57)
34.64
(18.13 to 51.16)
20.00
(2.41 to 37.59)
Change from Baseline at Week 13 Number Analyzed 58 participants 10 participants 9 participants
-31.10
(-36.78 to -25.42)
-30.00
(-46.83 to -13.17)
-6.35
(-33.24 to 20.54)
Change from Baseline at Week 25 Number Analyzed 58 participants 10 participants 8 participants
-30.73
(-35.88 to -25.58)
-29.64
(-46.03 to -13.26)
-17.86
(-37.85 to 2.14)
Change from Baseline at Week 37 Number Analyzed 57 participants 10 participants 7 participants
-31.20
(-36.66 to -25.75)
-31.07
(-46.45 to -15.69)
-21.94
(-43.97 to 0.09)
Change from Baseline at Week 49 Number Analyzed 56 participants 9 participants 7 participants
-28.76
(-34.33 to -23.20)
-29.37
(-45.94 to -12.79)
-22.96
(-45.75 to -0.17)
Change from Baseline at Week 57 Number Analyzed 41 participants 7 participants 6 participants
-27.79
(-33.94 to -21.63)
-32.65
(-50.38 to -14.92)
-26.19
(-54.20 to 1.82)
Change from Baseline at Week 81 Number Analyzed 32 participants 4 participants 4 participants
-31.36
(-39.13 to -23.59)
-23.21
(-51.25 to 4.82)
-13.39
(-49.74 to 22.96)
Change from Baseline at Week 105 Number Analyzed 20 participants 4 participants 4 participants
-27.86
(-40.08 to -15.64)
-18.75
(-59.83 to 22.33)
-16.96
(-44.17 to 10.24)
Change from Baseline at Week 129 Number Analyzed 16 participants 0 participants 0 participants
-27.01
(-41.30 to -12.72)
Change from Baseline at Week 153 Number Analyzed 7 participants 0 participants 0 participants
-30.10
(-45.58 to -14.63)
Change from Baseline at Week 177 Number Analyzed 6 participants 0 participants 0 participants
-32.14
(-61.17 to -3.11)
Change from Baseline at SC or ED Number Analyzed 52 participants 6 participants 4 participants
-30.29
(-36.26 to -24.32)
-35.12
(-58.99 to -11.25)
-21.43
(-79.38 to 36.53)
60.Secondary Outcome
Title Number of Participants With at Least One Adverse Event
Hide Description The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, are reported.
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
64
  94.1%
9
  90.0%
10
 100.0%
61.Secondary Outcome
Title Number of Participants With at Least One Grade ≥3 Adverse Event
Hide Description The World Health Organization (WHO) toxicity grading scale was used for assessing adverse event severity. For adverse events that are not specifically listed in the WHO toxicity grading scale, a grade 3 adverse event is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a grade 4 adverse event is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable.
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
15
  22.1%
1
  10.0%
3
  30.0%
62.Secondary Outcome
Title Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment
Hide Description [Not Specified]
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
  10.0%
63.Secondary Outcome
Title Number of Participants With at Least One Adverse Event of Local Injection Site Reaction
Hide Description Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction."
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
23
  33.8%
2
  20.0%
6
  60.0%
64.Secondary Outcome
Title Number of Participants With at Least One Adverse Event of Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction
Hide Description Systemic hypersensitivity, anaphylaxis, or anaphylactoid reactions were identified by the investigator using Sampson's criteria, as defined in the protocol. At the primary completion date, one participant had reported two non-serious adverse events (cough and abdominal pain) that were identified as a potential case based on a Standardised MedDRA Queries (SMQ) search for Sampson's criteria. However, after medical review of the case, it was confirmed that this case was not indicative of a systemic hypersensitivity, anaphylaxis, or anaphylactoid reaction.
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.5%
0
   0.0%
0
   0.0%
65.Secondary Outcome
Title Number of Participants With at Least One Adverse Event of Thromboembolic Event
Hide Description [Not Specified]
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
66.Secondary Outcome
Title Number of Participants With at Least One Adverse Event of Thrombotic Microangiopathy
Hide Description [Not Specified]
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
67.Secondary Outcome
Title Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADAs), Including Neutralizing ADAs, During the Study
Hide Description 'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample. ADA-positive samples were further analyzed for neutralizing capacity using a modified FVIII chromogenic assay; if also positive, they were considered neutralizing ADAs.
Time Frame Predose (0 hour) at Weeks 1, 5, 17, 33, 49, 57; then every 12 weeks until study completion (up to 188 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
Total ADA Negative (Neg + Neg Unaffected)
63
  92.6%
10
 100.0%
9
  90.0%
ADA Negative
59
  86.8%
10
 100.0%
9
  90.0%
ADA Negative (Treatment Unaffected)
4
   5.9%
0
   0.0%
0
   0.0%
Total ADA Positive (Boosted + Induced)
5
   7.4%
0
   0.0%
1
  10.0%
ADA Positive (Treatment Boosted)
0
   0.0%
0
   0.0%
0
   0.0%
ADA Positive (Treatment Induced)
5
   7.4%
0
   0.0%
1
  10.0%
ADA Positive with Neutralizing ADAs
2
   2.9%
0
   0.0%
1
  10.0%
68.Secondary Outcome
Title Number of Participants by Hematology Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Hide Description The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for hematology parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. Abs = absolute count
Time Frame From Baseline until study completion (up to 188 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
Hemoglobin, Low - Grade 0 to 0
53
  77.9%
10
 100.0%
9
  90.0%
Hemoglobin, Low - Grade 0 to 1
3
   4.4%
0
   0.0%
1
  10.0%
Hemoglobin, Low - Grade 0 to 2
4
   5.9%
0
   0.0%
0
   0.0%
Hemoglobin, Low - Grade 1 to 0
3
   4.4%
0
   0.0%
0
   0.0%
Hemoglobin, Low - Grade 1 to 1
4
   5.9%
0
   0.0%
0
   0.0%
Hemoglobin, Low - Grade 2 to 2
1
   1.5%
0
   0.0%
0
   0.0%
Neutrophils (Total, Abs), Low - Grade 0 to 0
39
  57.4%
7
  70.0%
9
  90.0%
Neutrophils (Total, Abs), Low - Grade 0 to 1
14
  20.6%
1
  10.0%
1
  10.0%
Neutrophils (Total, Abs), Low - Grade 0 to 2
5
   7.4%
2
  20.0%
0
   0.0%
Neutrophils (Total, Abs), Low - Grade 0 to 3
3
   4.4%
0
   0.0%
0
   0.0%
Neutrophils (Total, Abs), Low - Grade 0 to 4
1
   1.5%
0
   0.0%
0
   0.0%
Neutrophils (Total, Abs), Low - Grade 1 to 1
4
   5.9%
0
   0.0%
0
   0.0%
Neutrophils (Total, Abs), Low - Grade 1 to 2
1
   1.5%
0
   0.0%
0
   0.0%
Neutrophils (Total, Abs), Low - Grade 1 to 3
1
   1.5%
0
   0.0%
0
   0.0%
Platelets, Low - Grade 0 to 0
68
 100.0%
8
  80.0%
10
 100.0%
Platelets, Low - Grade 0 to 1
0
   0.0%
2
  20.0%
0
   0.0%
69.Secondary Outcome
Title Number of Participants by Chemistry Parameter Laboratory Test Results as a Shift From Baseline to Highest WHO Grade Post-Baseline
Hide Description The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for chemistry parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase
Time Frame From Baseline until study completion (up to 188 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of emicizumab
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Measure Type: Count of Participants
Unit of Measure: Participants
Alkaline Phosphatase, High - Grade 0 to 0
49
  72.1%
8
  80.0%
6
  60.0%
Alkaline Phosphatase, High - Grade 0 to 1
4
   5.9%
1
  10.0%
0
   0.0%
Alkaline Phosphatase, High - Grade 0 to 2
2
   2.9%
0
   0.0%
0
   0.0%
Alkaline Phosphatase, High - Grade 1 to 1
6
   8.8%
1
  10.0%
2
  20.0%
Alkaline Phosphatase, High - Grade 1 to 2
3
   4.4%
0
   0.0%
1
  10.0%
Alkaline Phosphatase, High - Grade 2 to 1
1
   1.5%
0
   0.0%
0
   0.0%
Alkaline Phosphatase, High - Grade 2 to 2
1
   1.5%
0
   0.0%
0
   0.0%
Alkaline Phosphatase, High - Missing to Grade 0
0
   0.0%
0
   0.0%
1
  10.0%
Alkaline Phosphatase, High - Missing to Grade 3
2
   2.9%
0
   0.0%
0
   0.0%
Bilirubin, High - Grade 0 to 0
62
  91.2%
10
 100.0%
10
 100.0%
Bilirubin, High - Grade 0 to 1
1
   1.5%
0
   0.0%
0
   0.0%
Bilirubin, High - Grade 0 to 2
2
   2.9%
0
   0.0%
0
   0.0%
Bilirubin, High - Missing to Grade 0
3
   4.4%
0
   0.0%
0
   0.0%
Blood Urea Nitrogen, High - Grade 0 to 0
58
  85.3%
10
 100.0%
9
  90.0%
Blood Urea Nitrogen, High - Grade 0 to 1
3
   4.4%
0
   0.0%
1
  10.0%
Blood Urea Nitrogen, High - Grade 1 to 1
3
   4.4%
0
   0.0%
0
   0.0%
Blood Urea Nitrogen, High - Missing to Grade 0
1
   1.5%
0
   0.0%
0
   0.0%
Blood Urea Nitrogen, High - Missing to Grade 1
1
   1.5%
0
   0.0%
0
   0.0%
Blood Urea Nitrogen, High - Missing to Grade 2
2
   2.9%
0
   0.0%
0
   0.0%
Calcium (Corrected), Low - Grade 0 to 0
54
  79.4%
7
  70.0%
9
  90.0%
Calcium (Corrected), Low - Grade 0 to 1
5
   7.4%
3
  30.0%
0
   0.0%
Calcium (Corrected), Low - Grade 0 to 2
2
   2.9%
0
   0.0%
0
   0.0%
Calcium (Corrected), Low - Grade 0 to 4
1
   1.5%
0
   0.0%
0
   0.0%
Calcium (Corrected), Low - Missing to Grade 0
5
   7.4%
0
   0.0%
1
  10.0%
Calcium (Corrected), Low - Missing to Grade 2
1
   1.5%
0
   0.0%
0
   0.0%
Calcium (Corrected), High - Grade 0 to 0
61
  89.7%
10
 100.0%
9
  90.0%
Calcium (Corrected), High - Grade 2 to 0
1
   1.5%
0
   0.0%
0
   0.0%
Calcium (Corrected), High - Missing to Grade 0
6
   8.8%
0
   0.0%
1
  10.0%
Creatinine, High - Grade 0 to 0
62
  91.2%
9
  90.0%
9
  90.0%
Creatinine, High - Grade 0 to 1
5
   7.4%
1
  10.0%
0
   0.0%
Creatinine, High - Grade 1 to 1
1
   1.5%
0
   0.0%
1
  10.0%
Glucose, Low - Grade 0 to 0
57
  83.8%
8
  80.0%
8
  80.0%
Glucose, Low - Grade 0 to 1
6
   8.8%
2
  20.0%
1
  10.0%
Glucose, Low - Grade 0 to 2
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, Low - Grade 0 to 3
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, Low - Grade 1 to 0
0
   0.0%
0
   0.0%
1
  10.0%
Glucose, Low - Grade 2 to 0
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, Low - Missing to Grade 0
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, Low - Missing to Grade 1
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, High - Grade 0 to 0
31
  45.6%
5
  50.0%
4
  40.0%
Glucose, High - Grade 0 to 1
28
  41.2%
3
  30.0%
6
  60.0%
Glucose, High - Grade 0 to 2
4
   5.9%
0
   0.0%
0
   0.0%
Glucose, High - Grade 1 to 0
1
   1.5%
1
  10.0%
0
   0.0%
Glucose, High - Grade 1 to 1
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, High - Grade 2 to 1
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, High - Grade 2 to 3
0
   0.0%
1
  10.0%
0
   0.0%
Glucose, High - Missing to Grade 0
1
   1.5%
0
   0.0%
0
   0.0%
Glucose, High - Missing to Grade 1
1
   1.5%
0
   0.0%
0
   0.0%
Magnesium, Low - Grade 0 to 0
57
  83.8%
9
  90.0%
9
  90.0%
Magnesium, Low - Grade 0 to 1
6
   8.8%
1
  10.0%
1
  10.0%
Magnesium, Low - Grade 4 to 1
1
   1.5%
0
   0.0%
0
   0.0%
Magnesium, Low - Missing to Grade 0
3
   4.4%
0
   0.0%
0
   0.0%
Magnesium, Low - Missing to Grade 2
1
   1.5%
0
   0.0%
0
   0.0%
Phosphorus, Low - Grade 0 to 0
64
  94.1%
10
 100.0%
10
 100.0%
Phosphorus, Low - Missing to Grade 0
4
   5.9%
0
   0.0%
0
   0.0%
Potassium, Low - Grade 0 to 0
61
  89.7%
9
  90.0%
10
 100.0%
Potassium, Low - Grade 0 to 1
5
   7.4%
1
  10.0%
0
   0.0%
Potassium, Low - Grade 0 to 2
1
   1.5%
0
   0.0%
0
   0.0%
Potassium, Low - Grade 1 to 0
1
   1.5%
0
   0.0%
0
   0.0%
Potassium, High - Grade 0 to 0
66
  97.1%
10
 100.0%
10
 100.0%
Potassium, High - Grade 0 to 1
1
   1.5%
0
   0.0%
0
   0.0%
Potassium, High - Grade 0 to 4
1
   1.5%
0
   0.0%
0
   0.0%
SGOT/AST, High - Grade 0 to 0
54
  79.4%
8
  80.0%
9
  90.0%
SGOT/AST, High - Grade 0 to 1
9
  13.2%
1
  10.0%
1
  10.0%
SGOT/AST, High - Grade 0 to 2
1
   1.5%
0
   0.0%
0
   0.0%
SGOT/AST, High - Grade 1 to 1
3
   4.4%
0
   0.0%
0
   0.0%
SGOT/AST, High - Missing to Grade 1
1
   1.5%
1
  10.0%
0
   0.0%
SGPT/ALT, High - Grade 0 to 0
52
  76.5%
10
 100.0%
9
  90.0%
SGPT/ALT, High - Grade 0 to 1
8
  11.8%
0
   0.0%
0
   0.0%
SGPT/ALT, High - Grade 0 to 2
4
   5.9%
0
   0.0%
0
   0.0%
SGPT/ALT, High - Grade 0 to 3
1
   1.5%
0
   0.0%
0
   0.0%
SGPT/ALT, High - Grade 1 to 1
2
   2.9%
0
   0.0%
1
  10.0%
SGPT/ALT, High - Missing to Grade 0
1
   1.5%
0
   0.0%
0
   0.0%
Sodium, Low - Grade 0 to 0
45
  66.2%
8
  80.0%
8
  80.0%
Sodium, Low - Grade 0 to 1
18
  26.5%
1
  10.0%
0
   0.0%
Sodium, Low - Grade 0 to 2
2
   2.9%
0
   0.0%
0
   0.0%
Sodium, Low - Grade 1 to 0
0
   0.0%
0
   0.0%
2
  20.0%
Sodium, Low - Grade 1 to 1
2
   2.9%
1
  10.0%
0
   0.0%
Sodium, Low - Grade 1 to 2
1
   1.5%
0
   0.0%
0
   0.0%
Sodium, High - Grade 0 to 0
58
  85.3%
9
  90.0%
10
 100.0%
Sodium, High - Grade 0 to 1
8
  11.8%
1
  10.0%
0
   0.0%
Sodium, High - Grade 0 to 2
1
   1.5%
0
   0.0%
0
   0.0%
Sodium, High - Grade 0 to 4
1
   1.5%
0
   0.0%
0
   0.0%
70.Secondary Outcome
Title Plasma Trough Concentration (Ctrough) of Emicizumab
Hide Description Pre-dose (trough) plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantitation was 0.1 micrograms per milliliter (μg/mL).
Time Frame Predose (0 hour) at Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, and 177
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of emicizumab and had at least one post-dose emicizumab plasma concentration result available
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Emicizumab Q2W Cohort C: 6 mg/kg Emicizumab Q4W
Hide Arm/Group Description:
Participants received emicizumab at a loading dose of 3 milligrams per kilogram (mg/kg) once every week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg QW SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 3 mg/kg once every 2 weeks (Q2W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Participants received emicizumab at a loading dose of 3 mg/kg QW subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 6 mg/kg once every 4 weeks (Q4W) SC for a minimum of 52 weeks, or until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria set forth in the protocol, whichever occurred first.
Overall Number of Participants Analyzed 68 10 10
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (μg/mL)
Week 1 Number Analyzed 67 participants 10 participants 10 participants
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Week 2 Number Analyzed 66 participants 10 participants 10 participants
18.2  (5.5) 17.0  (3.9) 17.2  (4.1)
Week 3 Number Analyzed 67 participants 10 participants 9 participants
31.6  (5.6) 31.7  (6.8) 33.9  (5.8)
Week 4 Number Analyzed 67 participants 10 participants 10 participants
42.9  (8.0) 42.4  (9.5) 44.7  (7.0)
Week 5 Number Analyzed 66 participants 10 participants 9 participants
53.3  (10.6) 51.8  (10.5) 56.4  (12.3)
Week 7 Number Analyzed 68 participants 10 participants 8 participants
51.2  (10.5) 51.5  (9.6) 59.9  (24.6)
Week 9 Number Analyzed 67 participants 10 participants 9 participants
49.9  (9.7) 51.9  (11.2) 39.3  (16.7)
Week 13 Number Analyzed 67 participants 10 participants 9 participants
48.3  (13.3) 45.3  (10.8) 37.1  (10.6)
Week 17 Number Analyzed 68 participants 10 participants 8 participants
46.1  (11.2) 48.7  (10.4) 36.3  (6.1)
Week 21 Number Analyzed 67 participants 10 participants 8 participants
45.2  (11.1) 43.9  (11.0) 36.2  (12.4)
Week 25 Number Analyzed 68 participants 10 participants 8 participants
46.9  (11.7) 41.9  (8.5) 33.7  (8.9)
Week 29 Number Analyzed 68 participants 9 participants 8 participants
47.9  (13.0) 46.7  (5.1) 34.4  (9.0)
Week 33 Number Analyzed 67 participants 10 participants 7 participants
51.3  (13.8) 51.0  (6.8) 34.7  (11.2)
Week 37 Number Analyzed 66 participants 9 participants 7 participants
51.0  (15.3) 50.4  (6.4) 35.9  (9.1)
Week 41 Number Analyzed 66 participants 10 participants 7 participants
48.5  (14.2) 55.3  (10.7) 38.1  (9.9)
Week 49 Number Analyzed 66 participants 10 participants 7 participants
49.4  (12.6) 48.6  (9.2) 32.4  (7.5)
Week 57 Number Analyzed 60 participants 9 participants 6 participants
46.2  (15.9) 46.4  (9.8) 28.5  (10.7)
Week 69 Number Analyzed 52 participants 4 participants 4 participants
46.4  (16.0) 54.7  (11.5) 41.1  (5.2)
Week 81 Number Analyzed 36 participants 4 participants 4 participants
45.6  (14.2) 38.0  (5.3) 35.7  (21.2)
Week 93 Number Analyzed 34 participants 4 participants 4 participants
44.3  (13.8) 41.2  (6.6) 41.6  (26.8)
Week 105 Number Analyzed 22 participants 4 participants 4 participants
46.9  (15.9) 43.4  (5.7) 34.2  (14.4)
Week 117 Number Analyzed 19 participants 4 participants 4 participants
37.8  (12.3) 46.6  (10.2) 37.1  (12.9)
Week 129 Number Analyzed 18 participants 0 participants 0 participants
39.7  (13.8)
Week 141 Number Analyzed 17 participants 0 participants 0 participants
46.5  (17.2)
Week 153 Number Analyzed 12 participants 0 participants 0 participants
39.5  (15.6)
Week 165 Number Analyzed 11 participants 0 participants 0 participants
39.9  (17.8)
Week 177 Number Analyzed 12 participants 0 participants 0 participants
38.9  (19.0)
[1]
No data available because the measurements were below the limit of quantitation.
Time Frame From Baseline up to 24 weeks after study drug discontinuation; the median (min-max) observation periods in Cohorts A, B, and C were 96.93 (36.1-188.1) weeks, 68.21 (56.7-129.4) weeks, and 69.43 (38.9-144.3) weeks, respectively.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort A: 1.5 mg/kg Emicizumab QW Cohort B: 3 mg/kg Em