Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A

Study Overview
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Brief Summary
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This Phase III clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in combination with prophylactic corticosteroids in patients with severe hemophilia A.

Official Title
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A Phase 3b, Single Arm, Open-Label Study to Evaluate the Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII, With Prophylactic Corticosteroids in Hemophilia A Patients

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, at the time of signing the informed consent. Must have been on prophylactic hemophilia therapy for at least 12 months prior to study entry. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs). No previous documented history of a detectable FVIII inhibitor, <0.6 Bethesda Units (BU). 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. Exclusion Criteria: Detectable pre-existing antibodies to the AAV5 capsid. Up to 25% of subjects may have detectable pre-existing AAV5 capsid antibodies, so long as the titer level is below the minimum required dilution (< 20). Any evidence of active infection or any immunosuppressive disorder; patients with HIV infection and undetectable viral load are not excluded. Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy. Evidence of any bleeding disorder not related to hemophilia A.

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<br>Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids | 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 in median FVIII activity as measured by chromogenic substrate assay, after administration of BMN 270 with prophylactic corticosteroids |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy or emicizumab for subjects receiving FVIII or emicizumab prophylaxis respectively after administration of BMN 270 with prophylactic corticosteroids |  | 52 weeks | 
| Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment after administration of BMN 270 with prophylactic corticosteroids |  | 52 weeks | 
| Impact of BMN 270 with prophylactic corticosteroids on quality of life as measured by the Haemo-QoL-A questionnaire | Haemo-QoL-A is a hemophilia-specific, health-related quality of life questionnaire for adults, which uses a scale from 0 (none of the time) to 5 (All of the time) to report data. | 52 weeks | 

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