Hemophilia A
Conditions
Keywords
prophylaxis treatment, Hemophilia A, Hemophilia, episodic treatment
Brief summary
The primary objective of the study was to evaluate the safety of rFVIIIFc (BIIB031) in previously untreated participants (PUPs) with severe hemophilia A. The secondary objectives were to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding episodes in PUPs, to evaluate rFVIIIFc consumption for the prevention and treatment of bleeding episodes in PUPs, and to describe experience with the use of rFVIIIFc for immune tolerance induction (ITI) in participants with inhibitors.
Interventions
BIOLOGICALrFVIIIFc
Administered as specified in arm description
Sponsors
Swedish Orphan Biovitrum
Bioverativ, a Sanofi company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 5 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Ability of the participant's legally authorized representative (e.g. their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations. * Weight \>=3.5 kg at the time of screening. * Severe hemophilia A defined as less than (\<) 1 IU/dL (\<1%) endogenous FVIII documented in the medical record or as tested during the Screening Period. Key
Exclusion criteria
* Any exposure to blood components, factor VIII replacement products, including commercially available rFVIIIFc at any time prior to or during screening. * History of positive inhibitor testing. A prior history of inhibitors was defined based on a patient's historical positive inhibitor test using the local laboratory Bethesda value for a positive inhibitor test (ie, equal to or above lower level of detection). * History of hypersensitivity reactions associated with any rFVIIIFc administration. * Other coagulation disorder(s) in addition to hemophilia A. * Any concurrent clinically significant major disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. * Current systemic treatment with chemotherapy and/or other immunosuppressant drugs. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay | Up to 3 years | A positive/confirmed inhibitor result occurs when a participant has a value \>=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected \>=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached \>=10 EDs and had \>=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received \>=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Number of Spontaneous Joint Bleeding Episodes | Up to 3 years | Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was no known contributing factor such as a definite trauma or antecedent strenuous activity. Annualized spontaneous joint bleeding episodes = (Total number of spontaneous joint bleeding episodes during EP divided by total 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 (\> 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study. |
| Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Up to 3 years | Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study. |
| Total Number of Exposure Days (EDs) | Up to 3 years | An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type. |
| Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes | Up to 3 years | Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)\*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (\>28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study. |
| Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR]) | Up to 3 years | ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized to a 1-year interval of time. Bleeding episodes were classified as spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent strenuous activity and as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)\*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study excluding surgical/rehabilitation periods and large injection intervals (greater than \[\>\]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study. |
| Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode | Up to 3 years | The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study. |
| Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 | Blood samples were taken at trough (predose) and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter \[IU/dL\] per IU/kg) = (Cmax for FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII activity less than (\<)0.5 IU/dL was set to 0 IU/dL for calculation of IR. |
| Number of Participants With Response to Immune Tolerance Induction (ITI) | Up to 3 years | Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR \>=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life \>=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI. |
| Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode | Up to 3 years | Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (\>28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study. |
Countries
Australia, Brazil, Canada, France, Germany, Ireland, Italy, Netherlands, New Zealand, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 44 active centers in 13 countries between 12-Jan-2015 to 23-Sep-2019.
Pre-assignment details
110 participants screened, 108 enrolled, 103 received drug.
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached \>= 50 exposure days (ED: 24-hour period in which \>=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (\>=5.00 BU/mL) or positive low titer inhibitor (\>=0.60 and \<5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding. | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| All Enrolled | Not Treated: Completed study in database | 2 |
| All Enrolled | Not Treated:Consent withdrawn by subject | 2 |
| All Enrolled | Not Treated: Exceeded lab value limit | 1 |
| All Treated | Death | 1 |
| All Treated | Exceeded lab value limit | 2 |
| All Treated | Lack of Efficacy | 3 |
| All Treated | Other | 7 |
| All Treated | Physician Decision | 5 |
Baseline characteristics
| Characteristic | Recombinant Coagulation Factor VIII Fc Fusion Protein |
|---|---|
| Age, Continuous | 0.58 years |
| Race/Ethnicity, Customized Asian | 5 Participants |
| Race/Ethnicity, Customized Black or African-American | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Not reported due to confidentiality regulations | 4 Participants |
| Race/Ethnicity, Customized Other | 11 Participants |
| Race/Ethnicity, Customized White | 79 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 103 |
| other Total, other adverse events | 85 / 103 |
| serious Total, serious adverse events | 60 / 103 |
Outcome results
Primary
Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
A positive/confirmed inhibitor result occurs when a participant has a value \>=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected \>=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached \>=10 EDs and had \>=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received \>=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.
Time frame: Up to 3 years
Population: Safety analysis set participants who 1) reached \>=10 EDs and had \>=1 inhibitor test performed at \>=10 EDs or who had inhibitor or 2) did not develop inhibitor but reached \>=10 EDs or 3) developed an inhibitor following the initial rFVIIIFc administration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay | 31.11 percentage of participants |
Secondary
Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized to a 1-year interval of time. Bleeding episodes were classified as spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent strenuous activity and as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)\*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study excluding surgical/rehabilitation periods and large injection intervals (greater than \[\>\]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time frame: Up to 3 years
Population: Analysis performed on Full Analysis Set (FAS) participants within the EP. FAS included all enrolled participants with \>=1 dose of study treatment. Here, number analyzed signifies number of FAS participants analyzed in each treatment regimen.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR]) | Episodic Treatment | 2.24 episodes per participant per year |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR]) | Prophylaxis Treatment | 1.49 episodes per participant per year |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR]) | ITI Treatment | 0.00 episodes per participant per year |
Secondary
Annualized Number of Spontaneous Joint Bleeding Episodes
Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was no known contributing factor such as a definite trauma or antecedent strenuous activity. Annualized spontaneous joint bleeding episodes = (Total number of spontaneous joint bleeding episodes during EP divided by total 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 (\> 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time frame: Up to 3 years
Population: Analysis was performed on FAS which included participants within EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Annualized Number of Spontaneous Joint Bleeding Episodes | Episodic Treatment | 0.00 episodes per participant per year |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Annualized Number of Spontaneous Joint Bleeding Episodes | Prophylaxis Treatment | 0.00 episodes per participant per year |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Annualized Number of Spontaneous Joint Bleeding Episodes | ITI Treatment | 0.00 episodes per participant per year |
Secondary
Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode
The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time frame: Up to 3 years
Population: Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode | Episodic Treatment | 45.45 IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode | Prophylaxis Treatment | 48.08 IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode | ITI Treatment | 189.44 IU/kg |
Secondary
Change From Baseline in rFVIIIFc Incremental Recovery (IR)
Blood samples were taken at trough (predose) and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter \[IU/dL\] per IU/kg) = (Cmax for FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII activity less than (\<)0.5 IU/dL was set to 0 IU/dL for calculation of IR.
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
Population: Analysis performed on FAS participants within the EP. Here number analyzed signifies number of FAS participants with available data for each visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 12 | -0.5 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 24 | -0.7 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 36 | -0.4 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 48 | -0.5 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 60 | -0.4 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 72 | -0.8 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 84 | -0.6 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 96 | -0.6 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 108 | -1.5 IU/dL per IU/kg |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Change From Baseline in rFVIIIFc Incremental Recovery (IR) | Change at Week 120 | -0.6 IU/dL per IU/kg |
Secondary
Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode
Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (\>28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time frame: Up to 3 years
Population: Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode | Episodic Treatment | 1.0 injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode | Prophylaxis Treatment | 1.0 injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode | ITI Treatment | 1.0 injections |
Secondary
Number of Participants With Response to Immune Tolerance Induction (ITI)
Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR \>=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life \>=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI.
Time frame: Up to 3 years
Population: Analysis performed on ITI analysis set which was defined as all participants who consented to and initiated the ITI sub-study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of Participants With Response to Immune Tolerance Induction (ITI) | Complete Success | 5 Participants |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of Participants With Response to Immune Tolerance Induction (ITI) | Partial Success | 2 Participants |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of Participants With Response to Immune Tolerance Induction (ITI) | Early Withdrawal | 3 Participants |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of Participants With Response to Immune Tolerance Induction (ITI) | ITI Ongoing at end of Study | 5 Participants |
Secondary
Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study.
Time frame: Up to 3 years
Population: Analysis performed on FAS participants within the EP and based on all injections. Here, number analyzed signifies number of responses to injections reported for each treatment regimen.
| Arm | Measure | Group | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Episodic Regimen | Excellent or Good | 102 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Episodic Regimen | Moderate | 16 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Episodic Regimen | None | 2 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Episodic Regimen | Response not provided | 118 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Prophylaxis Regimen | Excellent or Good | 163 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Prophylaxis Regimen | Moderate | 27 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Prophylaxis Regimen | None | 14 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | Prophylaxis Regimen | Response not provided | 89 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | ITI Regimen | Excellent or Good | 20 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | ITI Regimen | Moderate | 14 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | ITI Regimen | None | 3 responses to injections |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale | ITI Regimen | Response not provided | 11 responses to injections |
Secondary
Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)\*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (\>28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
Time frame: Up to 3 years
Population: Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes | Episodic Treatment | 197.6 IU per kilogram per participant per year |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes | Prophylaxis Treatment | 5384.4 IU per kilogram per participant per year |
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes | ITI Treatment | 67310.0 IU per kilogram per participant per year |
Secondary
Total Number of Exposure Days (EDs)
An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type.
Time frame: Up to 3 years
Population: Analysis performed on safety analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Coagulation Factor VIII Fc Fusion Protein | Total Number of Exposure Days (EDs) | 100.0 days |