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Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A (GENEr8-3)

Primary Purpose

Hemophilia A

Status
Active
Phase
Phase 3
Locations
International
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 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

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, at the time of signing the informed consent.
  2. Must have been on prophylactic hemophilia 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, <0.6 Bethesda Units (BU).
  5. 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:

  1. 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).
  2. Any evidence of active infection or any immunosuppressive disorder; patients with HIV infection and undetectable viral load are not excluded.
  3. Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy.
  4. Evidence of any bleeding disorder not related to hemophilia A.

Sites / Locations

  • Washington University School of Medicine
  • Nationwide Children's Hospital
  • The Royal Adelaide Hospital
  • Royal Brisbane and Women's Hospital
  • Alfred Hospital
  • Fiona Stanley Hospital
  • Royal Prince Alfred Hospital
  • Campinas University Clinical Hospital
  • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
  • Changhua Christian Medical Foundation Changhua Christian Hospital
  • Taichung Veterans General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

valoctocogene roxaparvovec

Arm Description

Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids

Outcomes

Primary Outcome Measures

Change in median FVIII activity as measured by chromogenic substrate assay, after administration of BMN 270 with prophylactic corticosteroids

Secondary Outcome Measures

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
Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment after administration of BMN 270 with prophylactic corticosteroids
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.

Full Information

First Posted
March 24, 2020
Last Updated
October 13, 2022
Sponsor
BioMarin Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT04323098
Brief Title
Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A
Acronym
GENEr8-3
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 10, 2020 (Actual)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
January 2027 (Anticipated)

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 evaluate the safety and effectiveness of valoctocogene roxaparvovec in combination with prophylactic corticosteroids in patients with severe hemophilia A.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
valoctocogene roxaparvovec
Arm Type
Experimental
Arm Description
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg with prophylactic corticosteroids
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 in median FVIII activity as measured by chromogenic substrate assay, after administration of BMN 270 with prophylactic corticosteroids
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
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
Time Frame
52 weeks
Title
Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment after administration of BMN 270 with prophylactic corticosteroids
Time Frame
52 weeks
Title
Impact of BMN 270 with prophylactic corticosteroids on quality of life as measured by the Haemo-QoL-A questionnaire
Description
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.
Time Frame
52 weeks

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, 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor, MD
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
The Royal Adelaide Hospital
City
Adelaide
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Perth
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Sydney
Country
Australia
Facility Name
Campinas University Clinical Hospital
City
Campinas
Country
Brazil
Facility Name
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
City
São Paulo
Country
Brazil
Facility Name
Changhua Christian Medical Foundation Changhua Christian Hospital
City
Changhua
Country
Taiwan
Facility Name
Taichung Veterans General Hospital
City
Taichung
Country
Taiwan

12. IPD Sharing Statement

Learn more about this trial

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

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