Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors

Inclusion criteria

• Males ≥ 18 years of age with hemophilia A and documented prior residual FVIII activity ≤ 1 IU/dL including, but not limited to, at the time of detected inhibitors, at the time of signing the informed consent.
• History of a positive inhibitor result with the first positive result at least 12 month prior to Screening.

Part A: Demonstrated no immunological tolerance to exogenous FVIII. Part B: Demonstrated tolerance to exogenous FVIII and negative FVIII inhibitor screening titer < 0.6 BU.

• Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor & hemophilia therapy Hx over previous 12 months.
• Sexually active participants must agree to use an acceptable method of effective contraception. Participants must agree to contraception use for at least 12 weeks post-infusion.
• Willing to abstain from consumption of alcohol for at least the first 52 weeks following BMN 270 infusion.

Exclusion criteria

• Detectable pre-existing antibodies to the AAV5 capsid.
• Any evidence of active infection or any immunosuppressive disorder; patients with HIV infection and undetectable viral load are not excluded.
• Currently undergoing, or plan to receive during the study, immune tolerance induction therapy or prophylaxis with FVIII (Part A only).
• Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy.
• Evidence of any bleeding disorder not related to hemophilia A.