Brief Title
Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5
Official Title
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
Brief Summary
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 Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
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.
Secondary Outcome
Efficacy of BMN 270 defined as FVIII activity at or above 5 IU/dL at Week 26.
Condition
Hemophilia A
Intervention
Valoctocogene Roxaparvovec
Study Arms / Comparison Groups
valoctocogene roxaparvovec Open Label
Description: Single administration of BMN270 at a dose of 6E13 vg/kg
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
10
Start Date
April 3, 2018
Completion Date
November 2026
Primary Completion Date
November 2026
Eligibility Criteria
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. Detectable pre-existing antibodies against the AAV5 vector capsid as measured by AAV5
total antibody ELISA.
3. Subject must have been on prophylactic FVIII replacement therapy for at least 12
months prior to study entry.
4. 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).
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. Any evidence of active infection including COVID-19, or any immunosuppressive
disorder, including HIV infection.
2. 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.
3. Chronic or active hepatitis B or C as evidenced by testing at screening.
4. Active malignancy, except non-melanoma skin cancer, or history of hepatic malignancy.
5. 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.
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Director, MD, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT03520712
Organization ID
BMN 270-203
Secondary IDs
2017-000662-29
Responsible Party
Sponsor
Study Sponsor
BioMarin Pharmaceutical
Study Sponsor
Medical Director, MD, Study Director, BioMarin Pharmaceutical
Verification Date
June 2021