Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A

Study Overview
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Brief Summary
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To compare the number of breakthrough bleeds under tailored prophylaxis with Human cell line recombinant factor FVIII (Human-cl rhFVIII) with the historical bleeding rate from patients who received Human-cl rhFVIII as on demand treatment.

Detailed Description
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There were 3 phases in this study: (1) An initial pharmacokinetic (PK) assessment in which participants received a single infusion of 60±5 IU/kg of Human-cl rhFVIII; blood samples were collected for 72 hours following the infusion. (2) Prophylactic Treatment-Phase I during which participants received infusions of 30-40 IU/kg of human-cl rhFVIII every other day or 3x/week for 1-3 months. (3) Prophylactic Treatment-Phase II during which the dose and dosing interval were determined individually from data gathered in the initial PK assessment. The maximum dosing interval with a dose of ≤ 60-80 IU/kg that maintains a trough level of ≥ 0.01 IU/mL was determined. Participants were treated for 6 months.

Official Title
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Prospective, Open-label, Multicenter Phase 3b Study to Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A

Conditions
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Severe Haemophilia A

Intervention / Treatment
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* Biological: Human-cl rhFVIII


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe haemophilia A (FVIII:C < 1%) according to medical history. Male patients ≥ 18 years old. Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 exposure days (EDs). Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start. Immunocompetence (CD4+ count > 200/microliter). HIV-negative, if positive, viral load < 200 particles/microliter or < 400,000 copies/mL. Freely given written informed consent Exclusion Criteria: Any coagulation disorder other than haemophilia A. Present or past FVIII inhibitor activity (> 0.6 Bethesda Unit [BU]) Severe liver or kidney disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human-cl rhFVIII<br>Up to 60-80 IU/kg of intravenous Human-cl rhFVIII was administered at an individually determined dose and dose interval. | Biological: Human-cl rhFVIII<br>* Human-cl rhFVIII was provided as a freeze-dried concentrate to be reconstituted in water for injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Number of Bleeding Episodes (BE) in Phase II | The annualized number of total BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196). | Beginning to the end of Phase II (6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II | The annualized number of spontaneous BEs was calculated for each participant as follows: d*y/t, where y = the number of spontaneous BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A spontaneous bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery and BEs due to trauma or due to other causes were not included. | Beginning to the end of Phase II (6 months) | 
| Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With ≤ 2 Treatments/Week | The annualized number of BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery were not included. | Beginning to the end of Phase II (6 months) | 
| Median Dosing Interval During Individually Tailored Prophylaxis | The median time between 2 prophylactic doses of Human-cl rhFVIII in the prophylactic treatment phase II were determined per patient | Beginning to the end of Phase II (6 months) | 
| Dosage Per Week in Phase II | The mean dosage per week during Phase II of the study are reported. | Beginning to the end of Phase II (6 months) |