Brief Title
Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)
Official Title
A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions
Brief Summary
This Phase III clinical study will assess the efficacy of BMN 270 defined as FVIII activity,
during weeks 49-52 following intravenous infusion of BMN 270 and assess the impact of BMN 270
on usage of exogenous FVIII replacement therapy and the number of bleeding episodes from week
5 to last visit by data cutoff.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Change from baseline in the median FVIII activity, as measured by chromogenic substrate assay, during Weeks 49-52 post-BMN 270 infusion
Secondary Outcome
Change from baseline in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy from Week 5 to last visit by data cut-off
Condition
Hemophilia A
Intervention
valoctocogene roxaparvovec
Study Arms / Comparison Groups
valoctocogene roxaparvovec Open Label
Description: Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
134
Start Date
December 19, 2017
Completion Date
November 2024
Primary Completion Date
November 16, 2020
Eligibility Criteria
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 AAV5 capsid.
2. Any evidence of active infection or any immunosuppressive disorder, including HIV
infection.
3. Significant liver dysfunction.
4. Prior liver biopsy showing significant fibrosis.
5. Evidence of any bleeding disorder not related to hemophilia A.
6. Platelet count of < 100 x 10^9/L.
7. Creatinine ≥ 1.5 mg/dL.
8. Liver cirrhosis of any etiology as assessed by liver ultrasound.
9. Chronic or active hepatitis B.
10. Active Hepatitis C.
11. Active malignancy, except non-melanoma skin cancer.
12. History of hepatic malignancy.
13. History of arterial or venous thromboembolic events.
14. Known inherited or acquired thrombophilia, including conditions associated with
increased thromboembolic risk, such as atrial fibrillation.
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Monitor, MD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT03370913
Organization ID
BMN 270-301
Secondary IDs
2017-003215-19
Responsible Party
Sponsor
Study Sponsor
BioMarin Pharmaceutical
Study Sponsor
Medical Monitor, MD, Study Director, BioMarin Pharmaceutical
Verification Date
October 2021