Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5

NCT ID: NCT03520712

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-24
• Study Completion Date: 2024-08-07

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.

Conditions

Hemophilia A; Gene Therapy; Clotting Disorders; Blood Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

valoctocogene roxaparvovec Open Label

Single administration of BMN270 at a dose of 6E13 vg/kg

Group Type: EXPERIMENTAL

Valoctocogene Roxaparvovec

Intervention Type: BIOLOGICAL

Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A

Interventions

Valoctocogene Roxaparvovec

Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A

Intervention Type: BIOLOGICAL

Other Intervention Names

BMN 270

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, 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center

Johannesburg, , South Africa

Kyung Hee University Hospital at Gangdong

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Royal Free Hospital

London, , United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Countries

South Africa; South Korea; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000662-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

270-203

Identifier Type: -

Identifier Source: org_study_id