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Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Pediatric Subjects With Hemophilia A (Kids ALONG)

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ClinicalTrials.gov Identifier: NCT01458106
Recruitment Status : Completed
First Posted : October 24, 2011
Results First Posted : December 12, 2014
Last Update Posted : September 25, 2018
Sponsor:
Collaborator:
Swedish Orphan Biovitrum
Information provided by (Responsible Party):
Bioverativ Therapeutics Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Interventions Drug: BIIB031 (rFVIIIFc)
Drug: FVIII (PK subgroup only)
Enrollment 71
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
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Pharmacokinetic (PK) subgroup: After a Washout Period of ≥72 hrs, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5±2 minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for PK assessment. Following a second Washout Period of ≥72 hrs, participants receive a single IV injection of rFVIIIFc over 5±2 mins at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Period Title: Overall Study
Started 36 35
PK Subgroup 25 35
Non-PK Subgroup 11 0
Completed 33 34
Not Completed 3 1
Reason Not Completed
Withdrawal by Subject             2             0
Pre-rFVIIIFc Adverse Event             1             0
Withdrawn Per Protocol             0             1
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old Total
Hide Arm/Group Description

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Total of all reporting groups
Overall Number of Baseline Participants 36 35 71
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 36 participants 35 participants 71 participants
4.0
(1 to 5)
8.0
(6 to 11)
5.0
(1 to 11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 35 participants 71 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
36
 100.0%
35
 100.0%
71
 100.0%
1.Primary Outcome
Title Occurrence of FVIII Inhibitor Development
Hide Description An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Incidences were summarized for any positive inhibitor for participants with ≥50 EDs to rFVIIIFc. In addition, the incidence for all participants, regardless of their EDs to rFVIIIFc, was also summarized. An exact 95% CI for the proportion of participants with a confirmed inhibitor was calculated using the Clopper-Pearson exact method for a binomial proportion.
Time Frame Up to Week 26 +/- 7 days, or up to 50 exposure days (EDs) if reached prior to Week 26
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Hide Analysis Population Description
Safety Analysis Set: participants who received at least 1 dose of prestudy FVIII, or at least 1 dose of rFVIIIFc; n=number of participants with given number of exposure days who had a valid inhibitor test.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old All Arms: Total
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

[Not Specified]
Overall Number of Participants Analyzed 36 35 71
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Participants with ≥50 EDs; n=27, 34, 61
0
(0 to 12.77)
0
(0 to 10.28)
0
(0 to 5.87)
All participants; n=36, 35, 71
0
(0 to 9.74)
0
(0 to 10.00)
0
(0 to 5.06)
2.Secondary Outcome
Title Annualized Bleeding Rate
Hide Description Annualized bleeding rate = (number of bleeding episodes during the efficacy period / total number of days during the efficacy period)*365.25. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last injection.
Time Frame Up to Week 26 +/- 7 days (efficacy period as defined in description)
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Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; based on the number of participants whose efficacy period was of at least 1 day in duration.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 35 34
Median (Inter-Quartile Range)
Unit of Measure: bleeding episodes per participant per yr
0.00
(0.00 to 3.96)
2.01
(0.00 to 4.04)
3.Secondary Outcome
Title Annualized Joint Bleeding Rate (Spontaneous)
Hide Description Annualized bleeding rate for spontaneous joint bleed=(number of bleeding episodes meeting those criteria during the efficacy period/total number of days during the efficacy period)*365.25. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last inject
Time Frame Up to Week 26 +/- 7 days (efficacy period as defined in description)
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Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; based on the number of participants whose efficacy period is of at least 1 day in duration.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 35 34
Median (Inter-Quartile Range)
Unit of Measure: bleeding episodes per participant per yr
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
4.Secondary Outcome
Title Participant Assessment of Response to Injections to Treat a Bleeding Episode
Hide Description Participant's assessment (provided by the caregiver) of the response to the first rFVIIIFc injection for each bleeding episode. Percentages were based on the number of first injections for which a response was provided, using the following 4-point scale: excellent=abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after the initial injection; good=definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection after 24 to 48 hours for complete resolution; moderate=probable or slight beneficial effect within approximately 8 hours after the initial injection and requiring more than one injection; no response=no improvement, or condition worsened, within approximately 8 hours after the initial injection.
Time Frame Up to Week 26 +/- 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc and had a bleeding episode; participants with a non-evaluable bleed are counted in the number of participants analyzed, but not the percentages.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 17 20
Overall Number of Units Analyzed
Type of Units Analyzed: Injections
35 46
Measure Type: Number
Unit of Measure: percent of 1st injections w/ a response
Excellent or Good 91.4 93.5
Excellent 65.7 47.8
Good 25.7 45.7
Moderate 8.6 2.2
No Response 0 4.3
5.Secondary Outcome
Title Physician’s Global Assessment of the Participant’s Response to His rFVIIIFc Regimen
Hide Description Investigators assessed each participant’s response to his rFVIIIFc regimen using a 4-point scale: excellent=bleeding episodes responded to ≤ the usual number of injections or ≤ the usual dose of rFVIIIFc or the rate of breakthrough bleeding during prophylaxis was ≤ that usually observed; effective=most bleeding episodes responded to the same number of injections and dose, but some required more injections or higher doses, or there was a minor increase in the rate of breakthrough bleeding; partially effective=bleeding episodes most often required more injections and/or higher doses than expected, or adequate breakthrough bleeding prevention during prophylaxis required more frequent injections and/or higher doses; ineffective=routine failure to control hemostasis, or hemostatic control required additional agents. Percentages are based on the total number of responses; multiple responses per participant are counted.
Time Frame Up to Week 26 +/- 7 days
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Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; based on the number of responses.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 35 34
Overall Number of Units Analyzed
Type of Units Analyzed: Responses
141 165
Measure Type: Number
Unit of Measure: percentage of responses
Excellent 96.5 89.7
Effective 3.5 9.1
Partially Effective 0 1.2
Ineffective 0 0
6.Secondary Outcome
Title Annualized rFVIIIFc Consumption Per Participant
Hide Description Consumption is calculated for the efficacy period. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. Annualized consumption = (total IU/kg of study treatment received during the efficacy period / total number of days during the efficacy period)*365.25. Consumption was calculated overall for all participants and for the last 3 months (91 days) on study, counted backwards from the end of the efficacy period, for participants with at least 24 weeks on study.
Time Frame Up to Week 26 +/- 7 days (efficacy period as defined in description)
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Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc. 'Overall' n=participants in the Full Analysis Set with evaluable data in the efficacy period; 'Last 3 Months on Study' n=participants in the Full Analysis Set with evaluable data and ≥ 24 weeks on study.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 35 34
Mean (Standard Deviation)
Unit of Measure: IU/kg rFVIIIFc per participant per year
Overall (n=35, 34) 5331.8  (1106.68) 4973.5  (976.06)
Last 3 months on study (n=26, 33) 5562.1  (1474.42) 5092.6  (1013.01)
7.Secondary Outcome
Title Number of Days From Last Treatment Injection to a Spontaneous Bleeding Episode
Hide Description The number of days from the last prophylaxis injection to the onset of a new spontaneous bleeding episode, analyzed across all evaluable bleeding episodes per participant and per episode, based on the efficacy period. Evaluable bleeding episodes are those for which both a date and time are available for both the onset of the bleeding episode and the previous prophylactic injection. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. For 'Per participant' values, the number of days from the last prophylactic injection to a spontaneous bleeding episode is averaged across all evaluable spontaneous bleeding episodes per participant.
Time Frame Up to Week 26 +/- 7 days (efficacy period as defined in description)
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Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; number of participants and number of episodes were determined for participants with at least 1 evaluable spontaneous bleeding episode.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 8 7
Overall Number of Units Analyzed
Type of Units Analyzed: Evaluable Spontaneous Bleeding Episodes
17 19
Median (Inter-Quartile Range)
Unit of Measure: days
Per Participant
2.17
(1.51 to 2.84)
2.55
(1.58 to 3.04)
Per Spontaneous Bleeding Episode
2.16
(1.35 to 2.87)
2.77
(1.58 to 3.29)
8.Secondary Outcome
Title Number of Injections Required for Resolution of a Bleeding Episode
Hide Description The number of injections required to resolve a bleeding episode per participant and per episode, based on the efficacy period. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. All injections given from the initial sign of a bleed, until the last date/time within the bleed window are counted. The resolution of a bleed is defined as no sign of bleeding following injection for the bleed. For 'Per participant' values, the number of injections required to resolve each bleed is averaged across all bleeding episodes per participant.
Time Frame Up to Week 26 +/- 7 days (efficacy period as defined in description)
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Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; number of participants and number of episodes were determined for participants with at least 1 evaluable bleeding episode.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 17 20
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding Episodes
38 48
Median (Inter-Quartile Range)
Unit of Measure: injections
Per Participant
1.0
(1.0 to 1.2)
1.0
(1.0 to 1.2)
Per Bleeding Episode
1.0
(1.0 to 1.0)
1.0
(1.0 to 1.0)
9.Secondary Outcome
Title Total Dose Required for Resolution of a Bleeding Episode
Hide Description The total dose required to resolve a bleeding episode per participant and per episode, based on the efficacy period. The efficacy period begins with the first prophylactic dose of rFVIIIFc and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. For 'Per bleeding episode' values, for each bleeding episode, the total dose is the sum of the doses (IU/kg) administered across all injections given to treat that bleeding episode. For 'Per participant' values, the total dose (IU/kg) used to resolve each bleed is averaged across all bleeding episodes per participant.
Time Frame Up to Week 26 +/- 7 days (efficacy period as defined in description)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: participants who received at least 1 dose of rFVIIIFc; number of participants and number of episodes were determined for participants who had complete information on the dose administered to treat a bleeding episode.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Overall Number of Participants Analyzed 17 20
Overall Number of Units Analyzed
Type of Units Analyzed: Bleeding Episodes
38 48
Median (Full Range)
Unit of Measure: IU/kg
Per Participant
55.56
(22.6 to 150.7)
51.35
(20.1 to 152.3)
Per Bleeding Episode
56.40
(13.9 to 200.0)
53.49
(14.0 to 196.6)
10.Secondary Outcome
Title Maximum Plasma Activity (Cmax; One-stage Activated Partial Thromboplastin Time [aPTT] Clotting Assay)
Hide Description Maximum plasma activity during a dosing interval for participants in the PK subgroup. The values for Cmax were adjusted to the nominal dose of 50 IU/kg. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
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Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/dL
95.03
(89.23 to 101.21)
114.94
(102.13 to 129.35)
11.Secondary Outcome
Title Maximum Plasma Activity (Cmax; Two-stage Chromogenic Assay)
Hide Description Maximum plasma activity during a dosing interval for participants in the PK subgroup. The values for Cmax were adjusted to the nominal dose of 50 IU/kg. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/dL
94.11
(86.40 to 102.51)
103.80
(95.68 to 112.60)
12.Secondary Outcome
Title Elimination Half Life (t1/2; One-stage aPTT Clotting Assay)
Hide Description Time required for the activity of the drug to reach half of its original value for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: hours
12.277
(10.988 to 13.718)
13.451
(11.445 to 15.808)
13.Secondary Outcome
Title Elimination Half Life (t1/2; Two-stage Chromogenic Assay)
Hide Description Time required for the activity of the drug to reach half of its original value for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: hours
14.268
(12.559 to 16.210)
15.861
(13.814 to 18.210)
14.Secondary Outcome
Title Clearance (CL; One-stage aPTT Clotting Assay)
Hide Description Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: mL/h/kg
3.4561
(3.0564 to 3.9080)
2.6067
(2.2559 to 3.0119)
15.Secondary Outcome
Title Clearance (CL; Two-stage Chromogenic Assay)
Hide Description Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: mL/h/kg
3.8600
(3.4839 to 4.2767)
3.0486
(2.6187 to 3.5491)
16.Secondary Outcome
Title Volume at Steady State (Vss; One-stage aPTT Clotting Assay)
Hide Description Volume of distribution at steady state for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: mL/kg
57.94
(54.13 to 62.01)
49.51
(44.08 to 55.60)
17.Secondary Outcome
Title Volume at Steady State (Vss; Two-stage Chromogenic Assay)
Hide Description Volume of distribution at steady state for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: mL/kg
66.48
(59.77 to 73.93)
63.15
(56.26 to 70.87)
18.Secondary Outcome
Title Dose Normalized Area Under the Curve (DNAUC; One-stage aPTT Clotting Assay)
Hide Description Dose normalized area under the FVIII activity-time curve for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU*h/dL per IU/kg
28.93
(25.59 to 32.72)
38.37
(33.20 to 44.35)
19.Secondary Outcome
Title Dose Normalized Area Under the Curve (DNAUC; Two-stage Chromogenic Assay)
Hide Description Dose normalized area under the FVIII activity-time curve for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU*h/dL per IU/kg
25.90
(23.38 to 28.69)
32.80
(28.18 to 38.19)
20.Secondary Outcome
Title Mean Residence Time (MRT; One-stage aPTT Clotting Assay)
Hide Description The average time that a drug molecule is present in the systemic circulation for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: hours
16.762
(15.106 to 18.599)
18.999
(16.213 to 22.263)
21.Secondary Outcome
Title Mean Residence Time (MRT; Two-stage Chromogenic Assay)
Hide Description The average time that a drug molecule is present in the systemic circulation for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: hours
17.220
(15.407 to 19.246)
20.708
(18.036 to 23.776)
22.Secondary Outcome
Title Incremental Recovery (IR; One-stage aPTT Clotting Assay)
Hide Description The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/dL per IU/kg
1.901
(1.785 to 2.024)
2.299
(2.042 to 2.587)
23.Secondary Outcome
Title Incremental Recovery (IR; Two-stage Chromogenic Assay)
Hide Description The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/dL per IU/kg
1.882
(1.728 to 2.050)
2.076
(1.914 to 2.252)
24.Secondary Outcome
Title Time at Maximum Activity (Tmax; One-stage aPTT Clotting Assay)
Hide Description Time at which maximum activity (Cmax) is observed for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: hours
0.6987
(0.5256 to 0.9287)
0.7257
(0.5685 to 0.9264)
25.Secondary Outcome
Title Time at Maximum Activity (Tmax; Two-stage Chromogenic Assay)
Hide Description Time at which maximum activity (Cmax) is observed for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: hours
0.7313
(0.5408 to 0.9889)
0.6334
(0.5184 to 0.7741)
26.Secondary Outcome
Title Lambda Z (One-stage aPTT Clotting Assay)
Hide Description First order rate constant associated with the terminal portion of the curve (lambda z) for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: 1/hours
0.05644
(0.05053 to 0.06304)
0.05158
(0.04390 to 0.06061)
27.Secondary Outcome
Title Lambda Z (Two-stage Chromogenic Assay)
Hide Description First order rate constant associated with the terminal portion of the curve (lambda z) for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: 1/hours
0.04848
(0.04264 to 0.05511)
0.04367
(0.03801 to 0.05018)
28.Secondary Outcome
Title Volume at Terminal Phase (Vz; One-stage aPTT Clotting Assay)
Hide Description Volume of distribution estimated from the terminal phase for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: mL/kg
61.22
(56.54 to 66.29)
50.58
(44.54 to 57.43)
29.Secondary Outcome
Title Volume at Terminal Phase (Vz; Two-stage Chromogenic Assay)
Hide Description Volume of distribution estimated from the terminal phase for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: mL/kg
79.48
(69.20 to 91.30)
69.75
(62.98 to 77.25)
30.Secondary Outcome
Title Area Under the Curve to the Last Measurable Timepoint (AUClast; One-stage aPTT Clotting Assay)
Hide Description Dose-normalized area under the FVIII activity-time curve to the last measurable timepoint for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU*h/dL
1410.4
(1254.8 to 1585.2)
1823.4
(1602.2 to 2075.0)
31.Secondary Outcome
Title Area Under the Curve to the Last Measurable Timepoint (AUClast; Two-stage Chromogenic Assay)
Hide Description Dose-normalized area under the FVIII activity-time curve to the last measurable timepoint for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
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Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU*h/dL
1250.1
(1133.2 to 1379.0)
1540.4
(1346.5 to 1762.3)
32.Secondary Outcome
Title Area Under the Curve to Infinity (AUCinf; One-stage aPTT Clotting Assay)
Hide Description Dose normalized area under the FVIII activity-time curve to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
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Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU*h/dL
1446.5
(1279.2 to 1635.7)
1918.5
(1660.0 to 2217.3)
33.Secondary Outcome
Title Area Under the Curve to Infinity (AUCinf; Two-stage Chromogenic Assay)
Hide Description Dose normalized area under the FVIII activity-time curve to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
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Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU*h/dL
1294.7
(1168.7 to 1434.3)
1640.0
(1408.7 to 1909.4)
34.Secondary Outcome
Title Percentage of AUCinf Extrapolated From the Last Data Point to Infinity (%AUCext; One-stage aPTT Clotting Assay)
Hide Description Percentage of AUCinf extrapolated from the last data point to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 23 31
Geometric Mean (95% Confidence Interval)
Unit of Measure: percentage of AUCinf
1.8421
(1.3218 to 2.5673)
2.7777
(1.9611 to 3.9344)
35.Secondary Outcome
Title Percentage of AUCinf Extrapolated From the Last Data Point to Infinity (%AUCext; Two-stage Chromogenic Assay)
Hide Description Percentage of AUCinf extrapolated from the last data point to infinity for participants in the PK subgroup. The 95% confidence interval on the geometric mean is based on the t-statistic back-transformed from the log scale.
Time Frame Baseline (28 ±7 days prior to Day 1) Prestudy FVIII Dosing: predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours post-dose. Day 1 (rFVIIIFc Dosing): predose; 30 ±5 min, 3 hours ±30 min, 24 ±3 hours, 48 ±4 hours, 72 ±7 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Analysis Set: All participants in the PK subgroup with adequate PK data, defined as complete and evaluable PK samples through 72 hours after rFVIIIFc dosing. Complete means the availability of the 72-hour sample and at least enough other samples to allow for all the PK parameters to be estimated.
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description:
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.
Overall Number of Participants Analyzed 24 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: percentage of AUCinf
2.7530
(2.1052 to 3.6001)
3.9476
(2.8296 to 5.5074)
Time Frame Serious adverse events (AEs): from informed consent up to 21 days after last treatment visit (LTV); AEs: from Baseline (28 ± 7 days prior to Day 1) for PK Subgroup or from Day 1 (first dose of rFVIIIFc) for non-PK subgroup, up to 14 (+7) days after LTV.
Adverse Event Reporting Description Length of rFVIIIFc dosing was up to 26 weeks ± 7 days. Serious and non-serious AEs that were treatment-emergent with respect to rFVIIIFc are presented for those participants who were treated with rFVIIIFc. Data are presented for the Full Analysis Set (participants who received at least 1 dose of rFVIIIFc).
 
Arm/Group Title Participants < 6 Years Old Participants 6 to < 12 Years Old
Hide Arm/Group Description

PK subgroup: After a Washout Period of ≥ 72 hours, at the Baseline Visit (28 ± 7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (± 2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥ 72 hours, participants receive a single IV injection of rFVIIIFc over 5 (± 2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

PK subgroup: After a Washout Period of ≥ 72 hours, at the Baseline Visit (28 ± 7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (± 2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥ 72 hours, participants receive a single IV injection of rFVIIIFc over 5 (± 2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

All-Cause Mortality
Participants < 6 Years Old Participants 6 to < 12 Years Old
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Participants < 6 Years Old Participants 6 to < 12 Years Old
Affected / at Risk (%) Affected / at Risk (%)
Total   4/35 (11.43%)   1/34 (2.94%) 
Infections and infestations     
Bacillus Infection  1  0/35 (0.00%)  1/34 (2.94%) 
Croup Infectious  1  1/35 (2.86%)  0/34 (0.00%) 
Escherichia Infection  1  0/35 (0.00%)  1/34 (2.94%) 
Metapneumovirus Infection  1  1/35 (2.86%)  0/34 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  1/35 (2.86%)  0/34 (0.00%) 
Head Injury  1  2/35 (5.71%)  0/34 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Participants < 6 Years Old Participants 6 to < 12 Years Old
Affected / at Risk (%) Affected / at Risk (%)
Total   31/35 (88.57%)   28/34 (82.35%) 
Ear and labyrinth disorders     
Ear Pain  1  2/35 (5.71%)  0/34 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain Upper  1  1/35 (2.86%)  4/34 (11.76%) 
Diarrhoea  1  3/35 (8.57%)  1/34 (2.94%) 
Vomiting  1  3/35 (8.57%)  2/34 (5.88%) 
General disorders     
Fatigue  1  1/35 (2.86%)  3/34 (8.82%) 
Pyrexia  1  1/35 (2.86%)  2/34 (5.88%) 
Immune system disorders     
Seasonal Allergy  1  2/35 (5.71%)  2/34 (5.88%) 
Infections and infestations     
Bronchitis  1  2/35 (5.71%)  0/34 (0.00%) 
Conjunctivitis Infective  1  0/35 (0.00%)  2/34 (5.88%) 
Ear Infection  1  2/35 (5.71%)  2/34 (5.88%) 
Gastroenteritis  1  2/35 (5.71%)  0/34 (0.00%) 
Nasopharyngitis  1  2/35 (5.71%)  4/34 (11.76%) 
Otitis Media  1  2/35 (5.71%)  0/34 (0.00%) 
Pharyngitis  1  2/35 (5.71%)  2/34 (5.88%) 
Tonsillitis  1  2/35 (5.71%)  2/34 (5.88%) 
Upper Respiratory Tract Infection  1  7/35 (20.00%)  2/34 (5.88%) 
Varicella  1  2/35 (5.71%)  0/34 (0.00%) 
Viral Upper Respiratory Tract Infection  1  3/35 (8.57%)  0/34 (0.00%) 
Injury, poisoning and procedural complications     
Face Injury  1  0/35 (0.00%)  2/34 (5.88%) 
Fall  1  3/35 (8.57%)  2/34 (5.88%) 
Head Injury  1  1/35 (2.86%)  2/34 (5.88%) 
Limb Injury  1  0/35 (0.00%)  2/34 (5.88%) 
Lip Injury  1  2/35 (5.71%)  0/34 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/35 (5.71%)  1/34 (2.94%) 
Joint Swelling  1  2/35 (5.71%)  1/34 (2.94%) 
Myalgia  1  0/35 (0.00%)  2/34 (5.88%) 
Pain In Extremity  1  2/35 (5.71%)  2/34 (5.88%) 
Nervous system disorders     
Headache  1  1/35 (2.86%)  4/34 (11.76%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  7/35 (20.00%)  6/34 (17.65%) 
Oropharyngeal Pain  1  0/35 (0.00%)  2/34 (5.88%) 
Rhinorrhoea  1  2/35 (5.71%)  1/34 (2.94%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
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.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Name/Title: Bioverativ Study Medical Director
Organization: Bioverativ
Responsible Party: Bioverativ Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01458106     History of Changes
Other Study ID Numbers: 8HA02PED
2011-003073-28
First Submitted: October 20, 2011
First Posted: October 24, 2011
Results First Submitted: December 4, 2014
Results First Posted: December 12, 2014
Last Update Posted: September 25, 2018