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

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

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.

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.

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.