Study of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) for On-demand Treatment of Bleeding Episodes in Patients With Hemophilia A or B With Inhibitors

A Multicenter, Open-label, Multiple-dose, Dose Escalation Study to Investigate the Pharmacokinetics, Efficacy, and Safety of rVIIa-FP (CSL 689) in Subjects With Hemophilia (A or B) and Inhibitors

The purpose of this study is to investigate the pharmacokinetics (PK), efficacy, and safety of rVIIa-FP (CSL689). The study will enroll approximately 54 male subjects, 12 to 65 years of age, with hemophilia types A or B who have developed inhibitors to FVIII or FIX. The study consists of 3 sequential parts (Parts 1, 2, 3): The purpose of Part 1 (PK part) is to evaluate the PK of a single treatment of CSL689 (low dose or high dose) and compare with the PK of a single treatment of Eptacog alfa (low dose or high dose). In Part 1, CSL689 and Eptacog alfa will be given by the doctor at the study center. The purpose of Part 2 (Dose-evaluation part) is to identify which of the 2 tested dose levels of CSL689 shows the best efficacy and safety in stopping acute bleeding events (this dose will be called the "population best dose"). The purpose of the final Part 3 (Repeated-dose part) is to confirm the efficacy and safety of the "population best dose" identified in Part 2. In Parts 2 and 3, subjects will self-administer a specified number of CSL689 infusions at home on-demand (ie, when a bleeding event occurs), will keep an electronic diary, and will visit the center at monthly intervals. This study is expected to last for up to 16 months for the subjects participating in all 3 parts, and up to 9 months for the subjects participating in Part 3 only.

Inclusion Criteria:

• Male subjects with hemophilia A or B and inhibitors.
• Age ≥ 12 and ≤ 65 years.
• High responding inhibitor with documented historical inhibitor titer > 5 Bethesda Units/mL.

Exclusion Criteria:

• Congenital or acquired coagulation disorders other than hemophilia A or B.
• Ongoing immune tolerance induction therapy or planned during study.
• Known or suspected hypersensitivity to activated recombinant human FVII or to any excipient of CSL689.
• Body mass index > 30 kg/m².
• Major surgery within 28 days before screening or scheduled major and / or orthopedic surgery during the study.
• Advanced atherosclerotic disease (ie, known history of ischemic heart disease, or ischemic stroke).
• Any clinical signs or known history of thromboembolic events, including known deep vein thrombosis.
• Human immunodeficiency virus (HIV)-positive subjects who have low cluster of differentiation 4 (CD4)+ lymphocyte count (200/μL or less) at screening.
• Use of the following within the screening period or planned during study: a) plasma or coagulation factor concentrates other than rescue therapy or therapy during Part 1, b) other platelet inhibitors, c) desmopressin, and d) fibrinolysis inhibitors, except if used as local treatment (eg, for oral bleeds).