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A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors (HAVEN 3)

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ClinicalTrials.gov Identifier: NCT02847637
Recruitment Status : Active, not recruiting
First Posted : July 28, 2016
Results First Posted : November 14, 2018
Last Update Posted : October 1, 2020
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Intervention Drug: Emicizumab
Enrollment 152
Recruitment Details  
Pre-assignment Details A total of 161 participants were screened, of which 9 failed screening and 152 who previously received either episodic or prophylactic treatment with FVIII agents were enrolled in this study. Participants in Arms A, B, and C were randomized in a 2:2:1 ratio; participants in Arm D were enrolled without randomization.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis. Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study. Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study. Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Period Title: Overall Study
Started 18 36 35 63
Completed 24 Weeks on No Prophylaxis 16 [1] 0 0 0
Switched to Emicizumab 3 mg/kg/2 Weeks 16 0 0 0
Completed 24 Weeks Emicizumab Treatment 1 [2] 35 34 58
Completed 1 1 0 0
Not Completed 17 35 35 63
Reason Not Completed
Withdrew from treatment due to AE             0             0             1             0
Ongoing treatment with emicizumab             16             35             34             63
First emicizumab dose delayed             1             0             0             0
[1]
One participant switched to emicizumab prior to completing 24 weeks No Prophylaxis (at 23.5 weeks).
[2]
Participants started on 24 weeks No Prophylaxis first before switching to emicizumab.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis) Total
Hide Arm/Group Description Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis. Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study. Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study. Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study. Total of all reporting groups
Overall Number of Baseline Participants 18 36 35 63 152
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 36 participants 35 participants 63 participants 152 participants
37.8  (12.9) 39.8  (14.0) 40.4  (11.4) 36.4  (14.4) 38.3  (13.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 36 participants 35 participants 63 participants 152 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
18
 100.0%
36
 100.0%
35
 100.0%
63
 100.0%
152
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 36 participants 35 participants 63 participants 152 participants
Hispanic or Latino
0
   0.0%
4
  11.1%
5
  14.3%
7
  11.1%
16
  10.5%
Not Hispanic or Latino
17
  94.4%
32
  88.9%
30
  85.7%
53
  84.1%
132
  86.8%
Unknown or Not Reported
1
   5.6%
0
   0.0%
0
   0.0%
3
   4.8%
4
   2.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 36 participants 35 participants 63 participants 152 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
4
  22.2%
6
  16.7%
10
  28.6%
12
  19.0%
32
  21.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   2.8%
0
   0.0%
0
   0.0%
1
   0.7%
Black or African American
3
  16.7%
3
   8.3%
1
   2.9%
1
   1.6%
8
   5.3%
White
11
  61.1%
24
  66.7%
20
  57.1%
47
  74.6%
102
  67.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
2
   5.6%
4
  11.4%
3
   4.8%
9
   5.9%
Number of Participants with <9 or ≥9 Bleeds in the Last 24 Weeks Prior to Study Entry  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 18 participants 36 participants 35 participants 63 participants 152 participants
Less Than (<) 9 Bleeds
4
  22.2%
9
  25.0%
5
  14.3%
53
  84.1%
71
  46.7%
Greater Than or Equal To (≥) 9 Bleeds
14
  77.8%
27
  75.0%
30
  85.7%
10
  15.9%
81
  53.3%
Number of Target Joints in the Last 24 Weeks Prior to Study Entry   [1] 
Mean (Standard Deviation)
Unit of measure:  Target joints
Number Analyzed 18 participants 36 participants 35 participants 63 participants 152 participants
2.2  (1.4) 2.1  (1.4) 2.2  (1.7) 1.0  (1.6) 1.7  (1.6)
[1]
Measure Description: A target joint was defined as at least 3 bleeds into the same joint over the last 24 weeks prior to study entry.
1.Primary Outcome
Title Annualized Bleeding Rate (ABR) for Treated Bleeds
Hide Description The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a negative binomial (NB) regression model, which accounts for different follow-up times, with the number of bleeds as a function of randomization and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. 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 the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
38.2
(22.86 to 63.76)
1.5
(0.89 to 2.47)
1.3
(0.75 to 2.25)
1.6
(1.07 to 2.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments H0 (null hypothesis): ABR Ratio for Arm A versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm A versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value was obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
0.020 to 0.075
Estimation Comments Arm A is the numerator and Arm C is the denominator for this ABR Ratio.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments H0 (null hypothesis): ABR Ratio for Arm B versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm B versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value was obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
0.017 to 0.066
Estimation Comments Arm B is the numerator and Arm C is the denominator for this ABR Ratio.
2.Secondary Outcome
Title Annualized Bleeding Rate (ABR) for All Bleeds
Hide Description The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: all bleed rate per year
47.6
(28.45 to 79.59)
2.5
(1.63 to 3.90)
2.6
(1.63 to 4.29)
3.3
(2.22 to 4.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments H0 (null hypothesis): ABR Ratio for Arm A versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm A versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value was obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.028 to 0.099
Estimation Comments Arm A is the numerator and Arm C is the denominator for this ABR Ratio.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments H0 (null hypothesis): ABR Ratio for Arm B versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm B versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value was obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
0.030 to 0.103
Estimation Comments Arm B is the numerator and Arm C is the denominator for this ABR Ratio.
3.Secondary Outcome
Title Annualized Bleeding Rate (ABR) for Treated Joint Bleeds
Hide Description The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A "joint bleed" is defined as a bleed 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. It is considered a "treated joint bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated joint bleed rate per year
26.5
(14.67 to 47.79)
1.1
(0.59 to 1.89)
0.9
(0.44 to 1.67)
1.2
(0.70 to 2.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments H0 (null hypothesis): ABR Ratio for Arm A versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm A versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value is obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
0.019 to 0.085
Estimation Comments Arm A is the numerator and Arm C is the denominator for this ABR Ratio.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments H0 (null hypothesis): ABR Ratio for Arm B versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm B versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value is obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
0.015 to 0.070
Estimation Comments Arm B is the numerator and Arm C is the denominator for this ABR Ratio.
4.Secondary Outcome
Title Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds
Hide Description The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. 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 is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded.
Time Frame From baseline to at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated spontaneous bleed rate per year
15.6
(7.60 to 31.91)
1.0
(0.48 to 1.91)
0.3
(0.11 to 0.75)
0.5
(0.23 to 0.94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments H0 (null hypothesis): ABR Ratio for Arm A versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm A versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value is obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
0.025 to 0.151
Estimation Comments Arm A is the numerator and Arm C is the denominator for this ABR Ratio.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments H0 (null hypothesis): ABR Ratio for Arm B versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm B versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level. The p-value is obtained via a global model with a 3-level categorical effect for treatment (emicizumab 1.5 mg/kg/week, emicizumab 3 mg/kg/2 weeks, or no prophylaxis).
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
0.006 to 0.056
Estimation Comments Arm B is the numerator and Arm C is the denominator for this ABR Ratio.
5.Secondary Outcome
Title Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds
Hide Description The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was assessed using a NB regression model, which accounts for different follow-up times, with the patient's number of bleeds as a function of randomization and the time that each patient stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes the number of bleeds (<9 or ≥9) in the last 24 weeks prior to study entry as a stratification factor. A "target joint bleed" is defined as a bleed reported as a joint bleed into a target joint, defined as at least 3 bleeds into the same joint during the last 24 weeks prior to study entry. It is considered a "treated target joint bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed". Bleeds due to surgery/procedure are excluded.
Time Frame From Baseline to at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants, which includes those randomized to Arms A, B, and C, and those enrolled in Arm D of the study.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated target joint bleed rate per year
13.0
(5.22 to 32.33)
0.6
(0.28 to 1.42)
0.7
(0.27 to 1.64)
0.6
(0.26 to 1.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments H0 (null hypothesis): ABR Ratio for Arm A versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm A versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Not controlled for type I error
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.016 to 0.143
Estimation Comments Arm A is the numerator and Arm C is the denominator for this ABR Ratio.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments H0 (null hypothesis): ABR Ratio for Arm B versus Arm C = 1. H1 (alternative hypothesis): ABR Ratio for Arm B versus Arm C ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Not controlled for type I error
Method Stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.018 to 0.147
Estimation Comments Arm B is the numerator and Arm C is the denominator for this ABR Ratio.
6.Secondary Outcome
Title Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With Factor VIII (FVIII) Prophylaxis (NISP)
Hide Description This is an intra-participant comparison of the annualized bleeding rate (ABR) for treated bleeds on study versus pre-study in the NIS population previously treated with FVIII prophylaxis in NIS BH29768. The number of treated bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. 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 the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded.
Time Frame 24 weeks prior to study entry, Baseline, through at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intra-participant comparison in the NIS population previously treated with FVIII prophylaxis (NISP), which includes all participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry in Arm D.
Arm/Group Title Dnisp: Pre-Study FVIII Prophylaxis in NIS BH29768 Dnisp: Emicizumab Prophylaxis (Pre-Study FVIII Prophylaxis)
Hide Arm/Group Description:
This arm includes historical data from participants in the non-interventional study (NIS) BH29768 who had received FVIII prophylaxis and were followed for a minimum of 24 weeks on the NIS prior to enrollment in Arm D of this study.
This arm includes data from the same participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry and then enrolled in Arm D of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg/week subcutaneously (SC) for 4 weeks, followed by emicizumab 1.5 mg/kg/week SC until the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Overall Number of Participants Analyzed 48 48
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
4.8
(3.22 to 7.09)
1.5
(0.98 to 2.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dnisp: Pre-Study FVIII Prophylaxis in NIS BH29768, Dnisp: Emicizumab Prophylaxis (Pre-Study FVIII Prophylaxis)
Comments H0 (null hypothesis): ABR Ratio = 1. H1 (alternative hypothesis): ABR Ratio ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level.
Method Non-stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.195 to 0.514
Estimation Comments Dnisp: Emicizumab Prophylaxis is the numerator and Dnisp: Pre-Study FVIII Prophylaxis is the denominator for this ABR ratio.
7.Secondary Outcome
Title Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the Non-Interventional Study Population Previously Treated With FVIII Prophylaxis (NISP)
Hide Description This is an intra-participant comparison of the annualized bleeding rate (ABR) for all bleeds on study versus pre-study in the NIS population previously treated with FVIII prophylaxis in NIS BH29768. The number of all bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the participant's number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded.
Time Frame 24 weeks prior to study entry, Baseline, through at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intra-participant comparison in the NIS population previously treated with FVIII prophylaxis (NISP), which includes all participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry in Arm D.
Arm/Group Title Dnisp: Pre-Study FVIII Prophylaxis in NIS BH29768 Dnisp: Emicizumab Prophylaxis (Pre-Study FVIII Prophylaxis)
Hide Arm/Group Description:
This arm includes historical data from participants in the non-interventional study (NIS) BH29768 who had received FVIII prophylaxis and were followed for a minimum of 24 weeks on the NIS prior to enrollment in Arm D of this study.
This arm includes data from the same participants who had received FVIII prophylaxis in NIS BH29768 prior to study entry and then enrolled in Arm D of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg/week subcutaneously (SC) for 4 weeks, followed by emicizumab 1.5 mg/kg/week SC until the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Overall Number of Participants Analyzed 48 48
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: all bleed rate per year
8.9
(5.72 to 13.87)
3.3
(2.17 to 5.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dnisp: Pre-Study FVIII Prophylaxis in NIS BH29768, Dnisp: Emicizumab Prophylaxis (Pre-Study FVIII Prophylaxis)
Comments H0 (null hypothesis): ABR Ratio = 1. H1 (alternative hypothesis): ABR Ratio ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level.
Method Non-stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.220 to 0.626
Estimation Comments Dnisp: Emicizumab Prophylaxis is the numerator and Dnisp: Pre-Study FVIII Prophylaxis is the denominator for this ABR ratio.
8.Secondary Outcome
Title Intra-Participant Comparison of ABR for Treated Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE)
Hide Description This is an intra-participant comparison of the annualized bleeding rate (ABR) for treated bleeds on study versus pre-study in the NIS population previously treated with episodic FVIII in NIS BH29768. The number of treated bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. 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 the time between treatment and the preceding bleed. Bleeds due to surgery/procedure are excluded.
Time Frame 24 weeks prior to study entry, Baseline, through at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intra-participant comparison in the NIS population previously treated with episodic FVIII (NISE), which includes all participants who had received episodic FVIII in NIS BH29768 prior to study entry in Arms A and B (pooled data).
Arm/Group Title A+Bnise: Pre-Study Episodic FVIII in NIS BH29768 A+Bnise: Emicizumab Prophylaxis (Pre-study Episodic FVIII)
Hide Arm/Group Description:
This arm includes historical data from participants in the non-interventional study (NIS) BH29768 who had received episodic FVIII treatment and were followed for a minimum of 24 weeks on the NIS prior to randomization to Arms A or B of this study. A pooled analysis, as opposed to two separate analyses, was performed due to the small number of NIS episodic patients (NISE) randomized to either Arm A or B.
This arm includes data from the same participants who had received episodic FVIII treatment in NIS BH29768 prior to study entry and then were randomized to Arms A or B of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg/week subcutaneously (SC) for 4 weeks, followed by either emicizumab 1.5 mg/kg/week SC (Arm A) or emicizumab 3 mg/kg/2 weeks SC (Arm B) until the end of study. A pooled analysis, as opposed to two separate analyses, was performed due to the small number of NIS episodic patients (NISE) randomized to either Arm A or B. The data reported was collected only during emicizumab prophylaxis treatment.
Overall Number of Participants Analyzed 20 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: treated bleed rate per year
34.4
(27.45 to 43.14)
1.0
(0.43 to 2.54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A+Bnise: Pre-Study Episodic FVIII in NIS BH29768, A+Bnise: Emicizumab Prophylaxis (Pre-study Episodic FVIII)
Comments H0 (null hypothesis): ABR Ratio = 1. H1 (alternative hypothesis): ABR Ratio ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Not controlled for type I error
Method Non-stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
0.014 to 0.067
Estimation Comments Arm A+Bnise: Emicizumab Prophylaxis is the numerator and Arm A+Bnise: Pre-Study Episodic FVIII is the denominator for this ABR Ratio.
9.Secondary Outcome
Title Intra-Participant Comparison of ABR for All Bleeds on Study Versus Pre-Study in Participants From the NIS Population Previously Treated With Episodic FVIII (NISE)
Hide Description This is an intra-participant comparison of the annualized bleeding rate (ABR) for all bleeds on study versus pre-study in the NIS population previously treated with episodic FVIII in NIS BH29768. The number of all bleeds over the efficacy period is presented as an ABR that was assessed using a NB regression model, which accounts for different follow-up times, with the participant's number of bleeds as a function of treatment and the time that each participant stays in the study (i.e., length of the efficacy period) included as an offset in the model. The model also includes a repeated statement to account for intra-participant comparison. "All bleeds" comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded.
Time Frame 24 weeks prior to study entry, Baseline, through at least 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intra-participant comparison in the NIS population previously treated with episodic FVIII (NISE), which includes all participants who had received episodic FVIII in NIS BH29768 prior to study entry in Arms A and B (pooled data).
Arm/Group Title A+Bnise: Pre-Study Episodic FVIII in NIS BH29768 A+Bnise: Emicizumab Prophylaxis (Pre-study Episodic FVIII)
Hide Arm/Group Description:
This arm includes historical data from participants in the non-interventional study (NIS) BH29768 who had received episodic FVIII treatment and were followed for a minimum of 24 weeks on the NIS prior to randomization to Arms A or B of this study. A pooled analysis, as opposed to two separate analyses, was performed due to the small number of NIS episodic patients (NISE) randomized to either Arm A or B.
This arm includes data from the same participants who had received episodic FVIII treatment in NIS BH29768 prior to study entry and then were randomized to Arms A or B of this study to receive emicizumab prophylaxis at a dose of 3 mg/kg/week subcutaneously (SC) for 4 weeks, followed by either emicizumab 1.5 mg/kg/week SC (Arm A) or emicizumab 3 mg/kg/2 weeks SC (Arm B) until the end of study. A pooled analysis, as opposed to two separate analyses, was performed due to the small number of NIS episodic patients (NISE) randomized to either Arm A or B. The data reported was collected only during emicizumab prophylaxis treatment.
Overall Number of Participants Analyzed 20 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: all bleed rate per year
39.6
(31.94 to 49.04)
1.6
(0.85 to 2.92)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A+Bnise: Pre-Study Episodic FVIII in NIS BH29768, A+Bnise: Emicizumab Prophylaxis (Pre-study Episodic FVIII)
Comments H0 (null hypothesis): ABR Ratio = 1. H1 (alternative hypothesis): ABR Ratio ≠ 1.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Not controlled for type I error
Method Non-stratified Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter ABR Ratio
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
0.023 to 0.068
Estimation Comments Arm A+Bnise: Emicizumab Prophylaxis is the numerator and Arm A+Bnise: Pre-Study Episodic FVIII is the denominator for this ABR Ratio.
10.Secondary Outcome
Title Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Physical Health Subscore for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25
Hide Description The Haem-A-QoL questionnaire has been developed and used in hemophilia A participants, assessing very specific aspects of dealing with hemophilia. The questionnaire consists of items pertaining to 10 domains: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain ranges from 0 to 100 with lower scores reflective of better quality of life. Physical Health domain score is reported (range 0 to 100, with lower scores reflective of better physical health). The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term.
Time Frame Baseline, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Adult participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Overall Number of Participants Analyzed 17 36 35
Mean (Standard Deviation)
Unit of Measure: units on a scale
44.32  (17.15) 31.81  (27.86) 28.35  (25.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0891
Comments Statistical significance is controlled at the 2-sided, 0.05 alpha level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 12.51
Confidence Interval (2-Sided) 95%
-1.96 to 26.98
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0349
Comments Not controlled for type I error
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 15.97
Confidence Interval (2-Sided) 95%
1.16 to 30.78
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm B.
11.Secondary Outcome
Title Haem-A-QoL Questionnaire Total Score for Adult Participants (≥18 Years of Age) in the Randomized Population at Week 25
Hide Description The Haem-A-QoL questionnaire has been developed and used in hemophilia A participants, assessing very specific aspects of dealing with hemophilia. The questionnaire consists of items pertaining to 10 domains: physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feeling, relationships, treatment, view of yourself, and outlook for the future. The total score for each domain ranges from 0 to 100 with lower scores reflective of better quality of life. Haem-A-QoL Total Score is the average of all domain scores and it ranges from 0 to 100, with lower scores reflective of better quality of life. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term.
Time Frame Baseline, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Adult participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Overall Number of Participants Analyzed 17 36 35
Mean (Standard Deviation)
Unit of Measure: units on a scale
29.95  (13.56) 24.04  (15.26) 21.39  (12.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1269
Comments Not controlled for type I error
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.91
Confidence Interval (2-Sided) 95%
-1.72 to 13.55
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0317
Comments Not controlled for type I error
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.56
Confidence Interval (2-Sided) 95%
0.77 to 16.35
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm B.
12.Secondary Outcome
Title European Quality of Life 5-Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score in the Randomized Population at Week 25
Hide Description EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L VAS. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term.
Time Frame Baseline, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35
Mean (Standard Deviation)
Unit of Measure: units on a scale
72.57  (8.20) 76.61  (20.99) 81.72  (15.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3402
Comments Not controlled for type I error
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.04
Confidence Interval (2-Sided) 95%
-12.43 to 4.35
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0373
Comments Not controlled for type I error
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.15
Confidence Interval (2-Sided) 95%
-17.74 to -0.55
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm B.
13.Secondary Outcome
Title EQ-5D-5L Questionnaire Index Utility Score in the Randomized Population at Week 25
Hide Description EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L VAS. The EQ-5D-5L health state profile is designed to record the participant's current health state in 5 domains: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. Responses from the five domains are used to calculate a single index utility score on a scale of 0 to 1, with higher scores reflective of better quality of life. The means were derived via an analysis of covariance (ANCOVA) model and have been adjusted for the following co-variates: baseline score, treatment group, and treatment by baseline interaction term.
Time Frame Baseline, Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
Participants randomized to Arms A, B, and C. The number analyzed represents participants who provided responses at Baseline and Week 25.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.63  (0.20) 0.76  (0.24) 0.76  (0.18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, A: Emicizumab 1.5 mg/kg/Week
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0060
Comments Not controlled for type I error
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.22 to -0.04
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection C: No Prophylaxis, B: Emicizumab 3 mg/kg/2 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0059
Comments Not controlled for type I error
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.23 to -0.04
Estimation Comments The difference in adjusted means was analyzed as Arm C minus Arm B.
14.Secondary Outcome
Title Hemophilia-Specific Quality of Life - Short Form (Haemo-QoL-SF) Questionnaire Score in Adolescent Participants (12 to 17 Years of Age) in the Randomized Population at Week 25
Hide Description The Haemo-QoL-SF 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. Haemo-QoL-SF total score range from 0 to 100, where lower scores reflect better health-related quality of life.
Time Frame Week 25
Hide Outcome Measure Data
Hide Analysis Population Description
The pre-specified efficacy objective was the comparison of Haemo-QoL-SF scores at Week 25 in adolescents who were previously on episodic treatment (i.e., randomized to Arms A, B, or C). Because there was a total of just one adolescent randomized to this study (in Arm C), statistical analyses could not be performed and no data is reported.
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Percentage of Participants With at Least One Adverse Event
Hide Description The percentage of participants experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
33.3 94.4 85.7 50.0 87.3
16.Secondary Outcome
Title Percentage of Participants With Grade ≥3 Adverse Events
Hide Description The World Health Organization (WHO) toxicity grading scale will be 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. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
5.6 8.3 11.4 0 9.3
17.Secondary Outcome
Title Percentage of Participants With Adverse Events Leading to Withdrawal From Treatment
Hide Description At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 2.9 0 0
18.Secondary Outcome
Title Percentage of Participants With Adverse Events of Changes From Baseline in Vital Signs
Hide Description The percentage of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0
19.Secondary Outcome
Title Percentage of Participants With Adverse Events of Changes From Baseline in Physical Examination Findings
Hide Description Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0
20.Secondary Outcome
Title Percentage of Participants With Adverse Events of Abnormal Laboratory Values
Hide Description The percentage of participants with adverse events of abnormal laboratory values is reported here. An abnormal laboratory value is defined as a laboratory test result outside of the normal range for hematology or serum chemistries. It is reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); results in a medical intervention or a change in concomitant therapy; or is clinically significant in the investigator's judgment. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0
21.Secondary Outcome
Title Percentage of Participants With Local Injection-Site Reactions
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." At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 25.0 20.0 12.5 33.3
22.Secondary Outcome
Title Percentage of Participants With Thromboembolic Events
Hide Description At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0
23.Secondary Outcome
Title Percentage of Participants With Thrombotic Microangiopathy
Hide Description At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0
24.Secondary Outcome
Title Percentage of Participants With Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reactions
Hide Description At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Arms A, B, and D who received at least one dose of emicizumab and all participants in Arm C who started the no prophylaxis study period. Participants in Arm Cemi are those from Arm C who switched after 24 weeks no prophylaxis to receive emicizumab prophylaxis (2 were excluded who did not switch at the time of analysis).
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 18 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0
25.Secondary Outcome
Title Percentage of Participants With Anti-Emicizumab Antibodies
Hide Description A validated ELISA method was used to analyze the levels of anti-emicizumab antibodies in plasma. A sample was considered positive for anti-emicizumab antibodies if the test result reached or exceeded a pre-determined threshold. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The All Emicizumab Population includes 150 participants in Arms A, B, Cemi, and D treated with emicizumab; 2 were excluded from Arm Cemi (1 lost to follow-up before Week 24; 1 had not switched to emicizumab prophylaxis at time of analysis).
Arm/Group Title A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0
26.Secondary Outcome
Title Percentage of Participants With De Novo Development of Factor VIII (FVIII) Inhibitors
Hide Description Levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold. At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame From Baseline up to 24 weeks after last dose of study drug (up to 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The All Emicizumab Population includes participants in Arms A, B, Cemi, and D treated with emicizumab; 2 were excluded from Arm Cemi (1 lost to follow-up before Week 24; 1 had not switched to emicizumab prophylaxis at time of analysis).
Arm/Group Title A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 36 35 16 63
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0
27.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) of Emicizumab
Hide Description 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). At the clinical cut-off date for primary analysis (15 Sep 2017), data was collected over a period of approximately 1 year.
Time Frame Predose (Hour 0) on every week during Weeks 1-4, every 2 weeks during Weeks 5-8, every 4 weeks during Weeks 9-24, every 8 weeks during Weeks 25-48, every 12 weeks thereafter up to the end of the study (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The All Emicizumab Population includes participants in Arms A, B, Cemi, and D treated with emicizumab; 2 participants who had not switched to emicizumab prophylaxis at time of analysis were excluded from Arm Cemi. Number analyzed represents participants per study arm with available samples at each specified timepoint.
Arm/Group Title A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description:
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study.
This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment.
Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
Overall Number of Participants Analyzed 36 35 16 63
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (μg/mL)
Week 1 Number Analyzed 35 participants 33 participants 0 participants 61 participants
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
Week 2 Number Analyzed 36 participants 35 participants 0 participants 61 participants
16.3  (6.1) 16.8  (5.9) 17.4  (5.4)
Week 3 Number Analyzed 36 participants 35 participants 0 participants 62 participants
29.1  (9.3) 29.2  (6.5) 30.5  (8.7)
Week 4 Number Analyzed 35 participants 34 participants 0 participants 60 participants
41.6  (11.9) 41.8  (9.5) 42.2  (9.4)
Week 5 Number Analyzed 34 participants 35 participants 0 participants 62 participants
48.0  (13.7) 48.8  (12.3) 54.5  (12.5)
Week 7 Number Analyzed 32 participants 33 participants 0 participants 60 participants
47.9  (16.1) 48.4  (11.4) 52.4  (13.4)
Week 9 Number Analyzed 33 participants 33 participants 0 participants 63 participants
49.0  (16.4) 47.1  (13.7) 55.1  (16.1)
Week 13 Number Analyzed 33 participants 31 participants 0 participants 59 participants
48.7  (18.3) 48.7  (15.6) 56.0  (15.7)
Week 17 Number Analyzed 31 participants 32 participants 0 participants 56 participants
51.7  (18.8) 49.6  (17.2) 55.4  (16.8)
Week 21 Number Analyzed 29 participants 33 participants 0 participants 58 participants
48.0  (17.7) 46.7  (15.3) 55.8  (16.3)
Week 25 Number Analyzed 28 participants 26 participants 13 participants 47 participants
51.0  (22.2) 46.3  (18.0) NA [1]   (NA) 55.0  (17.5)
Week 26 Number Analyzed 0 participants 0 participants 13 participants 0 participants
19.4  (9.2)
Week 27 Number Analyzed 0 participants 0 participants 12 participants 0 participants
32.9  (14.5)
Week 28 Number Analyzed 0 participants 0 participants 9 participants 0 participants
46.7  (17.4)
Week 29 Number Analyzed 0 participants 0 participants 9 participants 0 participants
59.2  (25.3)
Week 31 Number Analyzed 0 participants 0 participants 9 participants 0 participants
52.9  (17.3)
Week 33 Number Analyzed 12 participants 15 participants 7 participants 29 participants
61.8  (30.4) 47.6  (19.5) 47.0  (17.9) 59.9  (19.3)
Week 37 Number Analyzed 0 participants 0 participants 7 participants 0 participants
39.2  (17.6)
Week 41 Number Analyzed 6 participants 10 participants 4 participants 10 participants
45.2  (17.9) 47.1  (19.7) 40.3  (6.4) 54.9  (13.4)
Week 45 Number Analyzed 0 participants 0 participants 4 participants 0 participants
43.8  (9.4)
Week 49 Number Analyzed 2 participants 2 participants 0 participants 1 participants
62.3  (30.8) 43.6  (13.2) 54.1 [2]   (NA)
[1]
No data available because the measurements were below the limit of quantitation.
[2]
Standard deviation could not be calculated for single participant data.
Time Frame From Baseline up to the clinical cut-off date (15 Sep 2017) for primary analysis (approximately 1 year)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Hide Arm/Group Description Participants who had received episodic treatment with FVIII prior to study entry were randomized to continue episodic FVIII treatment when they started the trial; they were given the opportunity to switch to emicizumab prophylaxis after completing 24 weeks of no prophylaxis. Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study. Participants who had received episodic treatment with FVIII prior to study entry were randomized to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 3 mg/kg/2 weeks emicizumab SC until the end of study. This arm includes all participants from Arm C who switched to emicizumab prophylaxis after completing at least 24 weeks on No Prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg/week SC for the first 4 weeks (after at least 24 weeks) followed by a maintenance dose of 3 mg/kg/2 weeks SC up to the end of study. The data reported was collected only during emicizumab prophylaxis treatment. Participants who had received FVIII prophylaxis prior to study entry were enrolled to receive emicizumab prophylaxis at a dose of 3 mg/kg/week SC for 4 weeks, followed by 1.5 mg/kg/week emicizumab SC until the end of study.
All-Cause Mortality
C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/36 (0.00%)   0/35 (0.00%)   0/16 (0.00%)   0/63 (0.00%) 
Hide Serious Adverse Events
C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/18 (5.56%)   1/36 (2.78%)   3/35 (8.57%)   0/16 (0.00%)   8/63 (12.70%) 
Cardiac disorders           
Acute coronary syndrome † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Gastrointestinal disorders           
Mallory-Weiss syndrome † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Infections and infestations           
Infection † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Subperiosteal abscess † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Wound infection † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Injury, poisoning and procedural complications           
Femur fracture † 1  0/18 (0.00%)  0/36 (0.00%)  1/35 (2.86%)  0/16 (0.00%)  0/63 (0.00%) 
Musculoskeletal and connective tissue disorders           
Groin pain † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Rhabdomyolysis † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Synovitis † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Nervous system disorders           
Putamen haemorrhage † 1  0/18 (0.00%)  0/36 (0.00%)  1/35 (2.86%)  0/16 (0.00%)  0/63 (0.00%) 
Product Issues           
Device loosening † 1  0/18 (0.00%)  1/36 (2.78%)  0/35 (0.00%)  0/16 (0.00%)  0/63 (0.00%) 
Psychiatric disorders           
Suicidal ideation † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Respiratory, thoracic and mediastinal disorders           
Epistaxis † 1  0/18 (0.00%)  0/36 (0.00%)  1/35 (2.86%)  0/16 (0.00%)  1/63 (1.59%) 
Vascular disorders           
Haematoma † 1  1/18 (5.56%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/63 (0.00%) 
1
Term from vocabulary, MedDRA version 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
C: No Prophylaxis A: Emicizumab 1.5 mg/kg/Week B: Emicizumab 3 mg/kg/2 Weeks Cemi: Emicizumab 3 mg/kg/2 Weeks (Switch From No Prophylaxis) D: Emicizumab 1.5 mg/kg/Week (Pre-study FVIII Prophylaxis)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/18 (27.78%)   26/36 (72.22%)   23/35 (65.71%)   8/16 (50.00%)   43/63 (68.25%) 
Gastrointestinal disorders           
Abdominal pain † 1  0/18 (0.00%)  2/36 (5.56%)  0/35 (0.00%)  2/16 (12.50%)  1/63 (1.59%) 
Diarrhoea † 1  1/18 (5.56%)  1/36 (2.78%)  2/35 (5.71%)  1/16 (6.25%)  1/63 (1.59%) 
Nausea † 1  0/18 (0.00%)  0/36 (0.00%)  2/35 (5.71%)  0/16 (0.00%)  3/63 (4.76%) 
Vomiting † 1  1/18 (5.56%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/63 (0.00%) 
General disorders           
Injection site reaction † 1  0/18 (0.00%)  9/36 (25.00%)  7/35 (20.00%)  2/16 (12.50%)  20/63 (31.75%) 
Pain † 1  0/18 (0.00%)  0/36 (0.00%)  1/35 (2.86%)  1/16 (6.25%)  0/63 (0.00%) 
Immune system disorders           
Drug hypersensitivity † 1  0/18 (0.00%)  0/36 (0.00%)  2/35 (5.71%)  0/16 (0.00%)  0/63 (0.00%) 
Infections and infestations           
Conjunctivitis † 1  1/18 (5.56%)  1/36 (2.78%)  1/35 (2.86%)  0/16 (0.00%)  0/63 (0.00%) 
Influenza † 1  0/18 (0.00%)  1/36 (2.78%)  3/35 (8.57%)  0/16 (0.00%)  5/63 (7.94%) 
Gastric infection † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1/63 (1.59%) 
Localised infection † 1  1/18 (5.56%)  0/36 (0.00%)  1/35 (2.86%)  0/16 (0.00%)  0/63 (0.00%) 
Nasopharyngitis † 1  1/18 (5.56%)  2/36 (5.56%)  6/35 (17.14%)  0/16 (0.00%)  10/63 (15.87%) 
Pharyngitis † 1  0/18 (0.00%)  3/36 (8.33%)  1/35 (2.86%)  0/16 (0.00%)  2/63 (3.17%) 
Sinusitis † 1  1/18 (5.56%)  0/36 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1/63 (1.59%) 
Upper respiratory tract infection † 1  1/18 (5.56%)  4/36 (11.11%)  4/35 (11.43%)  0/16 (0.00%)  8/63 (12.70%) 
Injury, poisoning and procedural complications           
Bite † 1  1/18 (5.56%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/63 (0.00%) 
Contusion † 1  0/18 (0.00%)  2/36 (5.56%)  1/35 (2.86%)  0/16 (0.00%)  4/63 (6.35%) 
Excoriation † 1  1/18 (5.56%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/63 (0.00%) 
Muscle strain † 1  0/18 (0.00%)  2/36 (5.56%)  0/35 (0.00%)  0/16 (0.00%)  1/63 (1.59%) 
Laceration † 1  0/18 (0.00%)  1/36 (2.78%)  0/35 (0.00%)  1/16 (6.25%)  1/63 (1.59%) 
Ligament sprain † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  4/63 (6.35%) 
Tooth fracture † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1/63 (1.59%) 
Investigations           
Alanine aminotransferase increased † 1  0/18 (0.00%)  0/36 (0.00%)  2/35 (5.71%)  0/16 (0.00%)  0/63 (0.00%) 
Aspartate aminotransferase increased † 1  0/18 (0.00%)  0/36 (0.00%)  2/35 (5.71%)  0/16 (0.00%)  0/63 (0.00%) 
Blood creatine phosphokinase increased † 1  0/18 (0.00%)  0/36 (0.00%)  2/35 (5.71%)  1/16 (6.25%)  3/63 (4.76%) 
Musculoskeletal and connective tissue disorders           
Arthralgia † 1  1/18 (5.56%)  7/36 (19.44%)  6/35 (17.14%)  1/16 (6.25%)  14/63 (22.22%) 
Back pain † 1  1/18 (5.56%)  1/36 (2.78%)  1/35 (2.86%)  0/16 (0.00%)  0/63 (0.00%) 
Musculoskeletal stiffness † 1  1/18 (5.56%)  0/36 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/63 (0.00%) 
Pain in extremity † 1  1/18 (5.56%)  1/36 (2.78%)  3/35 (8.57%)  0/16 (0.00%)  3/63 (4.76%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Papilloma † 1  0/18 (0.00%)  0/36 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  0/63 (0.00%) 
Nervous system disorders           
Headache † 1  1/18 (5.56%)  3/36 (8.33%)  4/35 (11.43%)  1/16 (6.25%)  8/63 (12.70%) 
Psychiatric disorders           
Insomnia † 1  0/18 (0.00%)  1/36 (2.78%)  2/35 (5.71%)  0/16 (0.00%)  0/63 (0.00%) 
Skin and subcutaneous tissue disorders           
Pruritus † 1  0/18 (0.00%)  1/36 (2.78%)  1/35 (2.86%)  1/16 (6.25%)  1/63 (1.59%) 
1
Term from vocabulary, MedDRA version 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02847637    
Other Study ID Numbers: BH30071
2016-000072-17 ( EudraCT Number )
First Submitted: July 26, 2016
First Posted: July 28, 2016
Results First Submitted: September 14, 2018
Results First Posted: November 14, 2018
Last Update Posted: October 1, 2020