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

Purpose

This Phase III clinical study will assess the impact of BMN 270 (compared to FVIII prophylaxis) on the number of bleeding episodes irrespective of exogenous FVIII replacement treatment in the efficacy evaluation period (EEP) (from Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). The study will also assess the impact of BMN 270 (compared to FVIII prophylaxis) on: the number of bleeding episodes requiring exogenous FVIII treatment in "Post FVIII Prophylaxis to Last Visit", FVIII activity as measured by chromogenic sustrate assay at Week 104 following intravenous infusion of BMN 270, usage of exogenous FVIII replacement therapy in "Post FVIII Prophylaxis to Last Visit", health-related quality of life patient-reported outcomes at week 104 following intravenous infusion of BMN 270. The study will also evaluate the safety of the BMN 270.

Condition

  • Hemophilia A

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
valoctocogene roxaparvovec Open Label 		Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
  • Biological: valoctocogene roxaparvovec
    Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
    Other names:
    • BMN 270

More Details

Status
Active, not recruiting
Sponsor
BioMarin Pharmaceutical

Study Contact