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Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg (GENEr8-2)

Primary Purpose

Hemophilia A

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Valoctocogene Roxaparvovec
Sponsored by
BioMarin Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Males ≥ 18 years of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as evidenced by medical history.
  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.
  4. No previous documented history of a detectable FVIII inhibitor of less than 0.6 Bethesda Units (BU).

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, prior liver biopsy showing significant fibrosis, liver cirrhosis of any etiology or history of hepatic malignancy.
  4. Evidence of any bleeding disorder not related to hemophilia A.
  5. Active Hepatitis C.
  6. Prior treatment with any vector/gene transfer agent.

Sites / Locations

  • Hemophilia Center of Western Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Valoctocogene Roxaparvovec Open Label

Arm Description

Single administration of valoctocogene roxaparvovec at a dose of 4E13 vg/kg

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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

Full Information

First Posted
December 22, 2017
Last Updated
September 26, 2023
Sponsor
BioMarin Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT03392974
Brief Title
Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg
Acronym
GENEr8-2
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 at a Dose of 4E13vg/kg in Hemophilia A Patients With Residual FVIII Levels ≤1IU/dL Receiving Prophylactic FVIII Infusions
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
March 14, 2018 (Actual)
Primary Completion Date
May 22, 2019 (Actual)
Study Completion Date
June 5, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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 week 52.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
Keywords
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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Valoctocogene Roxaparvovec Open Label
Arm Type
Experimental
Arm Description
Single administration of valoctocogene roxaparvovec at a dose of 4E13 vg/kg
Intervention Type
Biological
Intervention Name(s)
Valoctocogene Roxaparvovec
Other Intervention Name(s)
BMN 270
Intervention Description
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Primary Outcome Measure Information:
Title
Change of the Median Factor VIII (FVIII) Activity
Description
Change of the FVIII activity, as measured by chromogenic substrate assay, at Week 52 post-BMN 270 infusion.
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
Change in the Annualized Utilization (IU/kg) of Exogenous FVIII Replacement Therapy
Description
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
Time Frame
Weeks 5 through Week 52
Title
Change in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment
Description
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
Time Frame
Weeks 5 though Week 52

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Biological males only
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director, MD
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
Facility Name
Hemophilia Center of Western Pennsylvania
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-4306
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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