Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)

Plain-language summary

This single-arm study evaluated the effectiveness and safety of a gene therapy called valoctocogene roxaparvovec in patients with hemophilia A. It enrolled men aged 18 and older with FVIII levels of ≤ 1 IU/dL who had been on preventive FVIII replacement therapy for at least 12 months. The trial was conducted in Phase 3 and has been completed.

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

Trial details

Phase

Phase 3

Status

Completed

Sponsor

BioMarin Pharmaceutical

Intervention

valoctocogene roxaparvovec

Start date

12/19/2017

Estimated completion

11/20/2024

Countries

United States, Australia, Belgium, Brazil, France, Germany, Israel, Italy, South Africa, South Korea, Spain, Taiwan, United Kingdom

Related genes

Locations

• Los Angeles, United States
• Sacramento, United States
• San Diego, United States
• San Francisco, United States
• Aurora, United States
• Tampa, United States
• Chicago, United States
• Louisville, United States
• New Orleans, United States
• Ann Arbor, United States
• Detroit, United States
• Minneapolis, United States
• St Louis, United States
• Chapel Hill, United States
• Columbus, United States
• Adelaide, Australia
• Brisbane, Australia
• Melbourne, Australia
• Perth, Australia
• Sydney, Australia
• Leuven, Belgium
• Campinas, Brazil
• Curitiba, Brazil
• Rio de Janeiro, Brazil
• São Paulo, Brazil
• Vitória, Brazil
• Lille, France
• Marseille, France
• Berlin, Germany
• Bonn, Germany
• Ramat Gan, Israel
• Milan, Italy
• Johannesburg, South Africa
• Seoul, South Korea
• A Coruña, Spain
• Seville, Spain
• Changhua, Taiwan
• Kaohsiung City, Taiwan
• Taichung, Taiwan
• Taipei, Taiwan

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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 residual FVIII levels ≤ 1 IU/dL as evidenced by medical history, at the time of signing the informed consent.
2. Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry.
3. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).
4. No previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least one week apart within the past 12 months.

Exclusion Criteria:

1. Detectable pre-existing antibodies to the adeno-associated virus 5 (AAV5) capsid.
2. Any evidence of active infection or any immunosuppressive disorder, except for HIV infection
3. Any evidence of active infection or any immunosuppressive disorder, including HIV infection (effective as of Protocol Amendment 3)
4. Significant liver dysfunction.
5. Prior liver biopsy showing significant fibrosis.
6. Evidence of any bleeding disorder not related to hemophilia A.
7. Platelet count of \< 100 x 10\^9/L.
8. Creatinine ≥ 1.5 mg/dL.
9. Liver cirrhosis of any etiology as assessed by liver ultrasound.
10. Chronic or active hepatitis B.
11. Active Hepatitis C.
12. Active malignancy, except non-melanoma skin cancer.
13. History of hepatic malignancy.
14. History of arterial or venous thromboembolic events.
15. Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.