Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg

Study Overview
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Brief Summary
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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 week 52.

Official Title
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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 at a Dose of 4E13vg/kg in Hemophilia A Patients With Residual FVIII Levels ≤1IU/dL Receiving Prophylactic FVIII Infusions

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: Valoctocogene Roxaparvovec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males ≥ 18 years of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as evidenced by medical history. Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days. No previous documented history of a detectable FVIII inhibitor of less than 0.6 Bethesda Units (BU). Exclusion Criteria: Detectable pre-existing antibodies to the AAV5 capsid. Any evidence of active infection or any immunosuppressive disorder, including HIV infection. Significant liver dysfunction, prior liver biopsy showing significant fibrosis, liver cirrhosis of any etiology or history of hepatic malignancy. Evidence of any bleeding disorder not related to hemophilia A. Active Hepatitis C. Prior treatment with any vector/gene transfer agent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valoctocogene Roxaparvovec Open Label<br>Single administration of valoctocogene roxaparvovec at a dose of 4E13 vg/kg | Biological: Valoctocogene Roxaparvovec<br>* Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A<br>* Other names: BMN 270;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the Median Factor VIII (FVIII) Activity | Change of the FVIII activity, as measured by chromogenic substrate assay, at Week 52 post-BMN 270 infusion. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Annualized Utilization (IU/kg) of Exogenous FVIII Replacement Therapy | Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy during Week 5 to Week 52 post-BMN 270 infusion from the baseline utilization of exogenous FVIII replacement therapy | Weeks 5 through Week 52 | 
| Change in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment | Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment (annualized bleeding rate, ABR) during Week 5 to Week 52 of the study post-BMN 270 infusion from the baseline ABR | Weeks 5 though Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Gene Therapy, Clotting Disorders, Blood Disorder, Blood Coagulation Disorders, Inherited Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn, Factor VIII, Coagulants