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

Plain-language summary

This Phase 1/2 study evaluated the safety and efficacy of valoctocogene roxaparvovec (BMN 270, GENEr8) gene therapy in patients with severe hemophilia A who have developed inhibitors to factor VIII (FVIII). Part A enrolled people with active FVIII inhibitors, while Part B involved people with a prior history of inhibitors. Eligibility required males aged 18 and over with hemophilia A, documented prior residual FVIII activity of 1 IU/dL or less, and a history of a positive inhibitor result.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Completed

Sponsor

BioMarin Pharmaceutical

Intervention

Valoctocogene roxaparvovec (BMN 270 (GENEr8))

Start date

12/10/2020

Estimated completion

4/20/2026

Countries

United States, Brazil, Israel, South Korea, Taiwan, Turkey (Türkiye), United Kingdom

Related genes

Locations

• Los Angeles, United States
• Campinas, Brazil
• Ramat Gan, Israel
• Seoul, South Korea
• Kaohsiung City, Taiwan
• Taichung, Taiwan
• Taipei, Taiwan
• Izmir, Turkey (Türkiye)
• London, United Kingdom

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

1. 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.
2. 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.
3. Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor \& hemophilia therapy Hx over previous 12 months.
4. 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.
5. Willing to abstain from consumption of alcohol for at least the first 52 weeks following BMN 270 infusion.

Exclusion Criteria:

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