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

NCT03520712 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 270-2032017-000662-29
• Study Type: interventional
• Target: 3
• Locations: 4 countries
• Sites: 9

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

Keywords

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Factor VIII; Coagulants; AAV5 antibodies

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events

  A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.

  Up to 5 years post-infusion.

Secondary Outcomes (4)

• Number of Participant With FVIII Activity >= 5 IU/dL at Week 26. Using Chromogenic Substrate Assay (CSA).

  26 weeks

• Mean Annualized Factor VIII Utilization During Week 5 and Beyond

  Week 5 and Beyond (Follow-Up, up to 1782 Days)

• Mean Annualized Factor VIII Infusion Rate During Week 5 and Beyond

  Week 5 and Beyond (Follow-Up, up to 1782 Days)

• Number of Participants Showed Reduction in the ABR Post-BMN 270 Infusion. Impact of BMN 270 on the Number of Bleeding Episodes Requiring Exogenous FVIII Therapy.

  Week 5 and Beyond (Follow-Up, up to 1782 Days)

Study Arms (1)

valoctocogene roxaparvovec Open Label

EXPERIMENTAL

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

Biological: Valoctocogene Roxaparvovec

Interventions

Valoctocogene Roxaparvovec BIOLOGICAL

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

Also known as: BMN 270

valoctocogene roxaparvovec Open Label

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Biological males only.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (9)

Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center

Johannesburg, South Africa

Location

Kyung Hee University Hospital at Gangdong

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Tri-Service General Hospital

Taipei, Taiwan

Location

Royal Free Hospital

London, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A; Hemostatic Disorders; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn

Interventions

Valoctocogene Roxaparvovec

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

In accordance with the study enrollment stopping criteria in the 270-203 study protocol and the Data Monitoring Committee (DMC) recommendation, decided to terminate 270-203, since 2 of the 3 participants in Cohort 1 (AAV5 TAb≤500) had FVIII activity 5IU/dL after a minimum of 6 weeks post-BMN 270 infusion. The last participant visit, and 270-203 termination, occurred on 07 August 2024.

Results Point of Contact

• Title: Konstantia-Maria Chavele, PhD, Director, Clinical Sciences
• Organization: BioMarin Pharmaceutical (UK) Ltd.

KonstantiaMaria.Chavele@bmrn.com

+44207

Study Officials

• Medical Director, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: May 11, 2018
• Study Start: April 24, 2018
• Primary Completion: August 7, 2024
• Study Completion: August 7, 2024
• Last Updated: August 22, 2025
• Results First Posted: August 22, 2025

Record last verified: 2025-08

Locations

KR (2); GB (2); ZA (1); TW (4)