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

Phase 1

Active, not recruiting

• Conditions: Hemophilia a; Gene Therapy; Clotting Disorders; Blood Disorder
• Interventions: Biological: Valoctocogene Roxaparvovec

• Registration Number: NCT03520712
• Lead Sponsor: BioMarin Pharmaceutical

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-04-03
• Study First Submitted: 2018-04-10
• Study First Submitted QC: 2018-04-27
• Study First Posted: 2018-05-11
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-22
• Last Update Posted: 2024-04-24
• Primary Completion: 2024-11
• Study Completion: 2024-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 3

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
valoctocogene roxaparvovec Open Label	Valoctocogene Roxaparvovec	Single administration of BMN270 at a dose of 6E13 vg/kg

Primary Outcome Measures

Name	Time	Method
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.	61 months

Secondary Outcome Measures

Name	Time	Method
Impact of BMN 270 on the number of bleeding episodes requiring exogenous FVIII therapy.	61 months
Efficacy of BMN 270 defined as FVIII activity at or above 5 IU/dL at Week 26.	26 weeks
Impact of BMN 270 on usage of exogenous FVIII replacement therapy.	61 months

Trial Locations

Locations (9)

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Kyung Hee University Hospital at Gangdong; 🇰🇷 Seoul, Korea, Republic of

Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center; 🇿🇦 Johannesburg, South Africa

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

Tri-Service General Hospital; 🇨🇳 Taipei, Taiwan

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, United Kingdom

Royal Free Hospital; 🇬🇧 London, United Kingdom

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of