Long-Term Safety and Efficacy of rFVIIIFc in the Prevention and Treatment of Bleeding Episodes in Previously Treated Participants With Hemophilia A
- Registration Number
- NCT01454739
- Lead Sponsor
- Bioverativ Therapeutics Inc.
- Brief Summary
The primary objective of the study is to evaluate the long-term safety of recombinant human Factor VIII Fc fusion protein (rFVIIIFc) in participants with hemophilia A. The secondary objective of the study is to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding episodes in participants with hemophilia A.
- Detailed Description
Participant will follow either a prophylaxis or on-demand regimen. The starting dose in this study will be determined by the clinical profile of the participant in the preceding studies A-LONG - 997HA301 (NCT01181128), pediatric study 8HA02PED (NCT01458106), 997HA307 (NCT02083965) and 997HA309 (NCT02502149).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 240
- Subjects who have completed previous rFVIIIFc studies (NCT01181128, NCT02083965, NCT01458106 and NCT02502149)
- Ability to understand purposes and risks of the study and to provide signed and dated informed consent (or assent, as applicable).
Key
- Confirmed positive high-titer inhibitor (≥5.00 BU/mL).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description On-Demand rFVIIIFc The individual dose of rFVIIIFc to treat bleeding episodes will be based on participant's clinical condition, type and severity of the bleeding event, and if indicated, Factor VIII (FVIII) levels. Prophylaxis rFVIIIFc Tailored prophylaxis, Weekly prophylaxis or Personalized prophylaxis available.
- Primary Outcome Measures
Name Time Method Number of Participants With Any Positive Inhibitor Development Approximately 5 years 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.
- Secondary Outcome Measures
Name Time Method Annualized Spontaneous Joint Bleeding Episodes Approximately 5 years 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.
Annualized Bleeding Rate (ABR) Approximately 5 years 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.
Annualized rFVIIIFc Consumption (International Units Per Kilogram [IU/kg]) Approximately 5 years 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.
Physicians' Global Assessment of Participant's Response to rFVIIIFc Regimen Using a 4-Point Scale Approximately 5 years 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.
Total Number of Exposure Days (EDs) Approximately 5 years 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.
Participant's Assessment of Response (Excellent or Good Response) to rFVIIIFc Injections for the Treatment of Bleeding Episodes Using a 4-Point Scale Approximately 5 years 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.
Trial Locations
- Locations (4)
Research Site
🇬🇧London, United Kingdom
Research site
🇳🇿Wellington, New Zealand
Children Cancer Centre
🇭🇰Hong Kong, New Territories, Hong Kong
Sir Yue Kong Pao Center for Cancer
🇭🇰Hong Kong, New Territories, Hong Kong