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Long-Term Safety and Efficacy of rFVIIIFc in the Prevention and Treatment of Bleeding Episodes in Previously Treated Participants With Hemophilia A (ASPIRE)

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ClinicalTrials.gov Identifier: NCT01454739
Recruitment Status : Completed
First Posted : October 19, 2011
Results First Posted : November 22, 2018
Last Update Posted : November 22, 2018
Sponsor:
Information provided by (Responsible Party):
Bioverativ Therapeutics Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia A
Intervention Drug: rFVIIIFc
Enrollment 240
Recruitment Details  
Pre-assignment Details Participants who completed studies 8HA02PED [NCT01458106], 997HA301 [NCT01181128]), 997HA307 (NCT02083965) and 997HA309 (NCT02502149) were expected to be eligible to enroll in this study.
Arm/Group Title rFVIIIFc (Participants From Study 8HA02PED) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309)
Hide Arm/Group Description Participants received rFVIIIFc intravenously (IV) per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P(WP): rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding prevention dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years, weekly and episodic treatment regimens were only available once reached at age of 12 years old. Participants received rFVIIIFc IV as per their assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 international unit per kilogram (IU/kg)-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding “prevention” dose prior to strenuous activity; targeting FVIII trough level of greater than (>)3 percent (%), if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Period Title: Overall Study
Started 61 [1] 179
Tailored Prophylaxis 59 131
Weekly Prophylaxis 0 34
Personalized Prophylaxis 3 23
Episodic 0 13
Surgery Subgroup [2] 2 26
Completed 54 158
Not Completed 7 21
Reason Not Completed
Protocol Violation             2             3
Withdrawal by Subject             2             6
Other             3             5
Physician Decision             0             5
Lost to Follow-up             0             1
Adverse Event             0             1
[1]
30 participants in <6 Years Old Age Cohort and 31 participants in 6 to <12 Years Old Age Cohort.
[2]
Participants who have undergone major surgery or have major surgical/rehabilitation period in study.
Arm/Group Title rFVIIIFc (Participants From Study 8HA02PED) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309) Total
Hide Arm/Group Description Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants less than (<)12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old. Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level. Total of all reporting groups
Overall Number of Baseline Participants 61 179 240
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 179 participants 240 participants
<18 years
61
 100.0%
22
  12.3%
83
  34.6%
Between 18 and 65 years
0
   0.0%
156
  87.2%
156
  65.0%
> 65 years
0
   0.0%
1
   0.6%
1
   0.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 179 participants 240 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
61
 100.0%
179
 100.0%
240
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 179 participants 240 participants
Hispanic or Latino
2
   3.3%
8
   4.5%
10
   4.2%
Not Hispanic or Latino
59
  96.7%
147
  82.1%
206
  85.8%
Unknown or Not Reported
0
   0.0%
24
  13.4%
24
  10.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 179 participants 240 participants
White
42
  68.9%
101
  56.4%
143
  59.6%
Black or African American
8
  13.1%
8
   4.5%
16
   6.7%
Asian
4
   6.6%
39
  21.8%
43
  17.9%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Other
7
  11.5%
7
   3.9%
14
   5.8%
Unknown or Not Reported
0
   0.0%
24
  13.4%
24
  10.0%
1.Primary Outcome
Title Number of Participants With Any Positive Inhibitor Development
Hide Description An inhibitor test result greater than or equal to (>=) 0.6 Bethesda units per milliliter (BU/mL), identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive. Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory. Data was summarized by treatment regimen for participants from 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame Approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included participants who received at least 1 dose of Recombinant Human Coagulation Factor VIII Fusion Protein(rFVIIIFc) in study 8HA01EXT.
Arm/Group Title rFVIIIFc (8HA02PED [<6 Years Old Age Cohort]) rFVIIIFc (8HA02PED [6 to <12 Years Old Age Cohort]) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309)
Hide Arm/Group Description:
Participants with < 6 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants with 6 to <12 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Overall Number of Participants Analyzed 30 31 179
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2.Secondary Outcome
Title Annualized Bleeding Rate (ABR)
Hide Description ABR is annualized number of bleeding episodes per participant per year. Bleeding episodes were classified as spontaneous if participant records bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity and as traumatic if participant records bleeding event when there is known reason for bleed. ABR=(Number of bleeding episodes during efficacy period (EP)/number of days during EP)*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. ABR was summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame Approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who received at least 1 dose of rFVIIIFc. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.
Arm/Group Title rFVIIIFc (8HA02PED [<6 Years Old Age Cohort]) rFVIIIFc (8HA02PED [6 to <12 Years Old Age Cohort]) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309)
Hide Arm/Group Description:
Participants with < 6 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants with 6 to <12 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Overall Number of Participants Analyzed 30 31 179
Median (Inter-Quartile Range)
Unit of Measure: episodes per participant per year
Tailored Prophylaxis Number Analyzed 29 participants 30 participants 131 participants
1.18
(0.60 to 2.37)
1.59
(0.55 to 3.55)
0.64
(0.00 to 2.84)
Weekly Prophylaxis Number Analyzed 0 participants 0 participants 34 participants
1.90
(0.27 to 4.85)
Personalized Prophylaxis Number Analyzed 2 participants 1 participants 23 participants
3.72
(3.35 to 4.09)
1.01
(1.01 to 1.01)
4.11
(0.64 to 8.78)
Episodic Number Analyzed 0 participants 0 participants 13 participants
19.10
(15.12 to 30.46)
3.Secondary Outcome
Title Annualized Spontaneous Joint Bleeding Episodes
Hide Description Bleeding episodes were classified as spontaneous if participant records a bleeding event when there is no known contributing factor such as definite trauma/antecedent strenuous activity. In addition, location of bleed (joint, internal, skin/mucosa or muscle) were collected. Annualized spontaneous joint bleeding episodes=(Number of spontaneous joint bleeding episodes during efficacy period (EP)/number of days during EP)*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Bleeding episodes were summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame Approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who received at least 1 dose of rFVIIIFc. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.
Arm/Group Title rFVIIIFc (8HA02PED [<6 Years Old Age Cohort]) rFVIIIFc (8HA02PED [6 to <12 Years Old Age Cohort]) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309)
Hide Arm/Group Description:
Participants with < 6 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants with 6 to <12 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Overall Number of Participants Analyzed 30 31 179
Median (Inter-Quartile Range)
Unit of Measure: episodes per participant per year
Tailored Prophylaxis Number Analyzed 29 participants 30 participants 131 participants
0.00
(0.00 to 0.55)
0.00
(0.00 to 0.55)
0.00
(0.00 to 0.63)
Weekly Prophylaxis Number Analyzed 0 participants 0 participants 34 participants
0.58
(0.00 to 1.90)
Personalized Prophylaxis Number Analyzed 2 participants 1 participants 23 participants
2.20
(1.34 to 3.07)
0.00
(0.00 to 0.00)
0.91
(0.00 to 2.84)
Episodic Number Analyzed 0 participants 0 participants 13 participants
9.22
(4.35 to 15.70)
4.Secondary Outcome
Title Total Number of Exposure Days (EDs)
Hide Description An exposure day is a 24-hour period in which one or more rFVIIIFc injections are given. The total number of days of exposure to rFVIIIFc were summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame Approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set included participants who received at least 1 dose of rFVIIIFc in study 8HA01EXT. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.
Arm/Group Title rFVIIIFc (8HA02PED [<6 Years Old Age Cohort]) rFVIIIFc (8HA02PED [6 to <12 Years Old Age Cohort]) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309)
Hide Arm/Group Description:
Participants with < 6 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants with 6 to <12 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Overall Number of Participants Analyzed 30 31 179
Median (Full Range)
Unit of Measure: days
Tailored Prophylaxis Number Analyzed 29 participants 30 participants 131 participants
287.00
(18.0 to 447.0)
373.00
(85.0 to 467.0)
257.00
(4.0 to 660.0)
Weekly Prophylaxis Number Analyzed 0 participants 0 participants 34 participants
203.50
(5.0 to 318.0)
Personalized Prophylaxis Number Analyzed 2 participants 1 participants 23 participants
127.00
(102.0 to 152.0)
107.0
(107.0 to 107.0)
223.00
(14.0 to 535.0)
Episodic Number Analyzed 0 participants 0 participants 13 participants
27.00
(0.0 to 88.0)
5.Secondary Outcome
Title Annualized rFVIIIFc Consumption (International Units Per Kilogram [IU/kg])
Hide Description Annualized consumption = (total international unit per kilogram [IU/kg] of study treatment received during the efficacy period / total number of days during the efficacy period) multiplied by 365.25. Efficacy period reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals. Annualized consumption was summarized by treatment regimen for participants from studies 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to <12 years old) and treatment regimen for participants from Study 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time Frame Approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants who received at least 1 dose of rFVIIIFc. Here 'n' (number analyzed) signifies number of participants who were analyzed in each treatment regimen, for each arm, respectively.
Arm/Group Title rFVIIIFc (8HA02PED [<6 Years Old Age Cohort]) rFVIIIFc (8HA02PED [6 to <12 Years Old Age Cohort]) rFVIIIFc[Participants From Studies 997HA301/997HA307/997HA309]
Hide Arm/Group Description:
Participants with < 6 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants with 6 to <12 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Overall Number of Participants Analyzed 30 31 179
Median (Inter-Quartile Range)
Unit of Measure: IU per kilogram per year
Tailored Prophylaxis Number Analyzed 29 participants 30 participants 131 participants
5417.9
(4683.4 to 6303.9)
4989.7
(4293.8 to 5842.4)
4359.8
(3993.8 to 5630.3)
Weekly Prophylaxis Number Analyzed 0 participants 0 participants 34 participants
3505.2
(3267.9 to 3639.0)
Personalized Prophylaxis Number Analyzed 2 participants 1 participants 23 participants
5457.1
(4435.0 to 6479.1)
4572.3
(4572.3 to 4572.3)
3926.7
(3261.8 to 6194.8)
Episodic Number Analyzed 0 participants 0 participants 13 participants
801.7
(286.2 to 1057.7)
6.Secondary Outcome
Title Physicians' Global Assessment of Participant's Response to rFVIIIFc Regimen Using a 4-Point Scale
Hide Description Participants were assessed for response to their rFVIIIFc regimen using following 4-point scale: 1=Excellent:bleeding episodes responded to less than or equal to (<=)usual number of injections/dose of rFVIIIFc or rate of breakthrough bleeding during prophylaxis was <= that usually observed; 2=Effective: most bleeding episodes responded to same number of injections and dose, but some required more injections or higher doses, or there was minor increase in rate of breakthrough; 3=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 and 4=Ineffective: routine failure to control hemostasis/hemostatic control require additional agents. Total number of scale responses =total count of scale responses for all participants; multiple responses per participant including those at scheduled and unscheduled visits are counted.
Time Frame Approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS- all participants who received at least 1 dose of rFVIIIFc. Data was summarized by treatment regimen for participants from 997HA301/997HA307/997HA309 combined and study from 8HA02PED per planned analysis. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Arm/Group Title rFVIIIFc (Participants From Study 8HA02PED) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309)
Hide Arm/Group Description:
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Overall Number of Participants Analyzed 61 179
Overall Number of Units Analyzed
Type of Units Analyzed: Responses
428 1252
Count of Units
Unit of Measure: Responses
Excellent
403
  94.2%
1061
  84.7%
Effective
24
   5.6%
186
  14.9%
Partially Effective
1
   0.2%
5
   0.4%
Ineffective
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Participant's Assessment of Response (Excellent or Good Response) to rFVIIIFc Injections for the Treatment of Bleeding Episodes Using a 4-Point Scale
Hide Description Using eDiary, participant received rating for treatment response to any bleeding episode (BE) using 4-point scale- 1=Excellent: Abrupt pain relief and/or improvement in signs of bleeding within approximately (approx.) 8 hours (h) after initial injection (inj.); 2=Good: Definite pain relief and/or improvement in signs of bleeding within approx. 8h after an injection, but possibly requiring more than 1 injection after 24–48h for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8h after initial injection and requires more than 1 injection and 4=None: No improvement, or condition worsens within approx. 8h after initial injection. This assessment was to be made approx. 8 to 12h from time the injection was given to treat BE and prior to any additional doses of rFVIIIFc given for same bleeding episode. Percentages are based on the number of bleeding episodes for which a response (excellent or good) was provided for the first injection during the efficacy period.
Time Frame Approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS was analyzed.Data was summarized by treatment regimen for participants from 997HA301/997HA307/997HA309 combined and by age cohort (<6 years and 6 to<12 years old) and treatment regimen for participants from 8HA02PED per planned analysis.Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Arm/Group Title rFVIIIFc (8HA02PED [<6 Years Old Age Cohort]) rFVIIIFc (8HA02PED [6 to <12 Years Old Age Cohort]) rFVIIIFc[Participants From Studies 997HA301/997HA307/997HA309]
Hide Arm/Group Description:
Participants with < 6 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants with 6 to <12 years old age received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old.
Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of greater than >3 %, if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level.
Overall Number of Participants Analyzed 30 31 179
Overall Number of Units Analyzed
Type of Units Analyzed: Injections
167 172 1734
Count of Units
Unit of Measure: Injections
Tailored Prophylaxis Number Analyzed 158 Injections 171 Injections 638 Injections
139
  88.0%
155
  90.6%
475
  74.5%
Weekly Prophylaxis Number Analyzed 0 Injections 0 Injections 341 Injections
260
  76.2%
Personalized Prophylaxis Number Analyzed 9 Injections 1 Injections 387 Injections
9
 100.0%
1
 100.0%
318
  82.2%
Episodic Number Analyzed 0 Injections 0 Injections 368 Injections
338
  91.8%
Time Frame From signing Informed Consent Form (ICF) through follow-up (approximately 5 years)
Adverse Event Reporting Description Adverse events (AEs) data was planned to be reported for each group and for the overall participants. AEs emergent during major surgical/rehabilitation periods are analyzed separately as per planned analysis and are presented as separate groups.
 
Arm/Group Title rFVIIIFc (Participants From Study 8HA02PED) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309) Overall(Participants From 8HA02PED/997HA301/997HA307/997HA309) Participants From Study 8HA02PED- Surgery Subgroup Participants From 997HA301/997HA307/997HA309- Surgery Subgroup
Hide Arm/Group Description Participants received rFVIIIFc IV per assigned treatment regimen as follows: Tailored Prophylaxis(TP): 25 IU/kg-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant’s needs (i.e. adding "prevention" dose prior to strenuous activity; targeting FVIII trough level of >3%, if bleeding history and/or activity level requires/dosing less frequently). Episodic (On demand): individual dose of rFVIIIFc based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). For participants <12 years of age, weekly and episodic treatment regimens were only available once reached at age of 12 years old. Participants received rFVIIIFc IV as per their assigned treatment regimen as follows: Tailored Prophylaxis (TP): 25 international unit per kilogram (IU/kg)-65 IU/kg rFVIIIFc every 3-5 days or 2 times/week at approximately 20 IU/kg to 65 IU/kg rFVIIIFc on Day 1 and 40 IU/kg-65 IU/kg rFVIIIFc on Day 4. Weekly P: rFVIIIFc once weekly at approximately 65 IU/kg. Personalized P: If optimal prophylaxis dosing not achieved using TP/WP, Investigator personalized dosing to meet individual participant's needs (options: adding “prevention” dose prior to strenuous activity; targeting FVIII trough level of greater than (>)3 percent (%), if bleeding history and/or activity level requires/dosing less frequently. Episodic (On demand): individual dose of rFVIIIFc IV based on clinical condition, type and severity of bleeding event and if indicated, FVIII levels (per investigator and Sponsor decision). The rate of administration determined by participant's comfort level. All participants who received rFVIIIFc drug in study 8HA01EXT, from studies 8HA02PED and 97HA301/997HA307/997HA309. AEs emergent during major surgical/rehabilitation periods are excluded and are presented as separate groups. Participants who required emergent or elective surgery while participating in this study and treated with the dose and regimen of rFVIIIFc as appropriate for the type of surgery. Participants returned to a regular rFVIIIFc regimen once all dosing for the postoperative rehabilitation period had been completed. Participants who required emergent or elective surgery while participating in this study and treated with the dose and regimen of rFVIIIFc as appropriate for the type of surgery. Participants returned to a regular rFVIIIFc regimen once all dosing for the postoperative rehabilitation period had been completed.
All-Cause Mortality
rFVIIIFc (Participants From Study 8HA02PED) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309) Overall(Participants From 8HA02PED/997HA301/997HA307/997HA309) Participants From Study 8HA02PED- Surgery Subgroup Participants From 997HA301/997HA307/997HA309- Surgery Subgroup
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/61 (0.00%)   0/179 (0.00%)   0/240 (0.00%)   0/2 (0.00%)   0/26 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
rFVIIIFc (Participants From Study 8HA02PED) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309) Overall(Participants From 8HA02PED/997HA301/997HA307/997HA309) Participants From Study 8HA02PED- Surgery Subgroup Participants From 997HA301/997HA307/997HA309- Surgery Subgroup
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   20/61 (32.79%)   43/179 (24.02%)   63/240 (26.25%)   0/2 (0.00%)   1/26 (3.85%) 
Cardiac disorders           
Acute myocardial infarction  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Angina pectoris  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Myocardial infarction  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Gastrointestinal disorders           
Abdominal pain upper  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Constipation  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Food poisoning  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Gastritis haemorrhagic  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Rectal haemorrhage  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Tooth impacted  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Varices oesophageal  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Vomiting  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
General disorders           
Device breakage  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Device dislocation  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Infusion site mass  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Pyrexia  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Hepatobiliary disorders           
Biliary colic  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Cholangitis acute  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Infections and infestations           
Appendicitis  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Cellulitis  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Chronic sinusitis  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Device related infection  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Hepatitis c  1  0/61 (0.00%)  2/179 (1.12%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Infectious pleural effusion  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Influenza  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Pericoronitis  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Pneumonia  1  1/61 (1.64%)  1/179 (0.56%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Sinusitis  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Staphylococcal bacteraemia  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Staphylococcal infection  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Streptococcal sepsis  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Subcutaneous abscess  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Tooth abscess  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Upper respiratory tract infection  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Viral infection  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Viral upper respiratory tract infection  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Injury, poisoning and procedural complications           
Accident  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Fall  1  6/61 (9.84%)  0/179 (0.00%)  6/240 (2.50%)  0/2 (0.00%)  0/26 (0.00%) 
Forearm fracture  1  2/61 (3.28%)  0/179 (0.00%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Head injury  1  6/61 (9.84%)  1/179 (0.56%)  7/240 (2.92%)  0/2 (0.00%)  0/26 (0.00%) 
Injury  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Joint dislocation  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Periprosthetic fracture  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Skull fracture  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Toxicity to various agents  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Transplant failure  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Traumatic haematoma  1  0/61 (0.00%)  2/179 (1.12%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Traumatic haemorrhage  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Post Procedural Haemorrhage  1  0/61 (0.00%)  0/179 (0.00%)  0/240 (0.00%)  0/2 (0.00%)  1/26 (3.85%) 
Investigations           
Body temperature increased  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Nuclear magnetic resonance imaging abnormal  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthropathy  1  0/61 (0.00%)  2/179 (1.12%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Haemarthrosis  1  2/61 (3.28%)  3/179 (1.68%)  5/240 (2.08%)  0/2 (0.00%)  0/26 (0.00%) 
Haemophilic arthropathy  1  0/61 (0.00%)  11/179 (6.15%)  11/240 (4.58%)  0/2 (0.00%)  0/26 (0.00%) 
Intervertebral disc disorder  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Osteoarthritis  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Spinal osteoarthritis  1  0/61 (0.00%)  2/179 (1.12%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Synovitis  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Hepatic neoplasm malignant  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Metastases to peritoneum  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Nervous system disorders           
Cubital tunnel syndrome  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Headache  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Hydrocephalus  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Nerve compression  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Psychiatric disorders           
Depression  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Renal and urinary disorders           
Calculus ureteric  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Haematuria  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Nephrolithiasis  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Renal impairment  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Epistaxis  1  1/61 (1.64%)  1/179 (0.56%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Nasal polyps  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Skin and subcutaneous tissue disorders           
Haemorrhage subcutaneous  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Urticaria  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Surgical and medical procedures           
Bone graft  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Carpal tunnel decompression  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Central venous catheter removal  1  4/61 (6.56%)  0/179 (0.00%)  4/240 (1.67%)  0/2 (0.00%)  0/26 (0.00%) 
Central venous catheterisation  1  2/61 (3.28%)  1/179 (0.56%)  3/240 (1.25%)  0/2 (0.00%)  0/26 (0.00%) 
Circumcision  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Joint arthroplasty  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Knee arthroplasty  1  0/61 (0.00%)  2/179 (1.12%)  2/240 (0.83%)  0/2 (0.00%)  0/26 (0.00%) 
Vascular disorders           
Bleeding varicose vein  1  0/61 (0.00%)  1/179 (0.56%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Superior vena cava syndrome  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
Superior vena caval stenosis  1  1/61 (1.64%)  0/179 (0.00%)  1/240 (0.42%)  0/2 (0.00%)  0/26 (0.00%) 
1
Term from vocabulary, MedDRA 15.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
rFVIIIFc (Participants From Study 8HA02PED) rFVIIIFc(Participants From Studies 997HA301/997HA307/997HA309) Overall(Participants From 8HA02PED/997HA301/997HA307/997HA309) Participants From Study 8HA02PED- Surgery Subgroup Participants From 997HA301/997HA307/997HA309- Surgery Subgroup
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   49/61 (80.33%)   110/179 (61.45%)   159/240 (66.25%)   0/2 (0.00%)   4/26 (15.38%) 
Gastrointestinal disorders           
Diarrhoea  1  5/61 (8.20%)  16/179 (8.94%)  21/240 (8.75%)  0/2 (0.00%)  0/26 (0.00%) 
Vomiting  1  8/61 (13.11%)  6/179 (3.35%)  14/240 (5.83%)  0/2 (0.00%)  0/26 (0.00%) 
Constipation  1  0/61 (0.00%)  0/179 (0.00%)  0/240 (0.00%)  0/2 (0.00%)  2/26 (7.69%) 
General disorders           
Pyrexia  1  6/61 (9.84%)  5/179 (2.79%)  11/240 (4.58%)  0/2 (0.00%)  0/26 (0.00%) 
Immune system disorders           
Seasonal allergy  1  9/61 (14.75%)  5/179 (2.79%)  14/240 (5.83%)  0/2 (0.00%)  0/26 (0.00%) 
Infections and infestations           
Gastroenteritis viral  1  6/61 (9.84%)  2/179 (1.12%)  8/240 (3.33%)  0/2 (0.00%)  0/26 (0.00%) 
Influenza  1  3/61 (4.92%)  14/179 (7.82%)  17/240 (7.08%)  0/2 (0.00%)  0/26 (0.00%) 
Nasopharyngitis  1  6/61 (9.84%)  37/179 (20.67%)  43/240 (17.92%)  0/2 (0.00%)  0/26 (0.00%) 
Pharyngitis  1  4/61 (6.56%)  2/179 (1.12%)  6/240 (2.50%)  0/2 (0.00%)  0/26 (0.00%) 
Tonsillitis  1  12/61 (19.67%)  2/179 (1.12%)  14/240 (5.83%)  0/2 (0.00%)  0/26 (0.00%) 
Upper respiratory tract infection  1  13/61 (21.31%)  19/179 (10.61%)  32/240 (13.33%)  0/2 (0.00%)  0/26 (0.00%) 
Viral infection  1  4/61 (6.56%)  3/179 (1.68%)  7/240 (2.92%)  0/2 (0.00%)  0/26 (0.00%) 
Viral upper respiratory tract infection  1  7/61 (11.48%)  0/179 (0.00%)  7/240 (2.92%)  0/2 (0.00%)  0/26 (0.00%) 
Injury, poisoning and procedural complications           
Fall  1  11/61 (18.03%)  14/179 (7.82%)  25/240 (10.42%)  0/2 (0.00%)  0/26 (0.00%) 
Laceration  1  1/61 (1.64%)  15/179 (8.38%)  16/240 (6.67%)  0/2 (0.00%)  0/26 (0.00%) 
Limb injury  1  4/61 (6.56%)  10/179 (5.59%)  14/240 (5.83%)  0/2 (0.00%)  0/26 (0.00%) 
Postoperative fever  1  0/61 (0.00%)  0/179 (0.00%)  0/240 (0.00%)  0/2 (0.00%)  2/26 (7.69%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  7/61 (11.48%)  20/179 (11.17%)  27/240 (11.25%)  0/2 (0.00%)  0/26 (0.00%) 
Pain in extremity  1  5/61 (8.20%)  11/179 (6.15%)  16/240 (6.67%)  0/2 (0.00%)  0/26 (0.00%) 
Nervous system disorders           
Headache  1  10/61 (16.39%)  15/179 (8.38%)  25/240 (10.42%)  0/2 (0.00%)  0/26 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  8/61 (13.11%)  9/179 (5.03%)  17/240 (7.08%)  0/2 (0.00%)  0/26 (0.00%) 
Vascular disorders           
Hypertension  1  0/61 (0.00%)  9/179 (5.03%)  9/240 (3.75%)  0/2 (0.00%)  0/26 (0.00%) 
1
Term from vocabulary, MedDRA 15.0
Indicates events were collected by systematic assessment
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 Therapeutics Inc.
Phone: 781-6631801
Responsible Party: Bioverativ Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01454739     History of Changes
Other Study ID Numbers: 8HA01EXT
2011-003072-37
First Submitted: September 29, 2011
First Posted: October 19, 2011
Results First Submitted: October 5, 2018
Results First Posted: November 22, 2018
Last Update Posted: November 22, 2018