- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03520712
Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5 (GENEr8-AAV5+)
April 22, 2024 updated by: BioMarin Pharmaceutical
A Phase 1/2 Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL and Pre-existing Antibodies Against AAV5
This study is being conducted by BioMarin Pharmaceutical Inc. as an open label, single dose study to determine the safety of valoctocogene roxaparvovec (an Adenovirus-Associated Virus (AAV) based gene therapy vector) in severe Hemophilia A patients with pre-existing antibodies against AAV5.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
3
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Seoul, Korea, Republic of
- Kyung Hee University Hospital at Gangdong
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Seoul, Korea, Republic of
- Severance Hospital, Yonsei University Health System
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Johannesburg, South Africa
- Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center
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Kaohsiung, Taiwan
- Kaohsiung Medical University Chung-Ho Memorial Hospital
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Taichung, Taiwan
- Taichung Veterans General Hospital
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Taipei, Taiwan
- Tri-Service General Hospital
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Taipei, Taiwan
- National Taiwan University Hospital
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London, United Kingdom
- Royal Free Hospital
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Southampton, United Kingdom
- University Hospital Southampton NHS Foundation Trust
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
- Detectable pre-existing antibodies against the AAV5 vector capsid as measured by AAV5 total antibody ELISA.
- Subject must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry.
- 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) (or less than 1.0 BU for laboratories with a historical lower sensitivity cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week apart within the past 12 months (at least one of which should be tested at the central laboratory).
- 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:
- Any evidence of active infection including COVID-19, or any immunosuppressive disorder, except for HIV infection. HIV positive patients who meet all other eligibility criteria may be included if they have a CD4 count > 200/mm3 and an undetectable viral load (unquantifiable viral load as defined as less than the limit of quantification by the testing laboratory's assay is permitted) while receiving an antiretroviral therapy (ART) regimen that does not contain efavirenz or another potentially hepatotoxic ART.
- Evidence of liver dysfunction as assessed by liver tests and most recent, prior FibroScan or liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
- Chronic or active hepatitis B or C as evidenced by testing at screening.
- Active malignancy, except non-melanoma skin cancer, or history of hepatic malignancy.
- Any condition that, in the opinion of the investigator or Sponsor would prevent the patient from fully complying with the requirements of the study (including corticosteroid treatment and/or use of alternative immunosuppressive agents outlined in the protocol) and/or would impact or interfere with evaluation and interpretation of subject safety or efficacy result.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: valoctocogene roxaparvovec Open Label
Single administration of BMN270 at a dose of 6E13 vg/kg
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Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Safety of a single intravenous administration of BMN 270 in severe HA subjects with pre-existing antibody to AAV5 vector capsid, including development of FVIII neutralizing antibody.
Time Frame: 61 months
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61 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Efficacy of BMN 270 defined as FVIII activity at or above 5 IU/dL at Week 26.
Time Frame: 26 weeks
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26 weeks
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Impact of BMN 270 on usage of exogenous FVIII replacement therapy.
Time Frame: 61 months
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61 months
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Impact of BMN 270 on the number of bleeding episodes requiring exogenous FVIII therapy.
Time Frame: 61 months
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61 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Director, MD, BioMarin Pharmaceutical
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 3, 2018
Primary Completion (Estimated)
November 1, 2024
Study Completion (Estimated)
November 1, 2024
Study Registration Dates
First Submitted
April 10, 2018
First Submitted That Met QC Criteria
April 27, 2018
First Posted (Actual)
May 11, 2018
Study Record Updates
Last Update Posted (Actual)
April 24, 2024
Last Update Submitted That Met QC Criteria
April 22, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 270-203
- 2017-000662-29 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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