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Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5 (270-203)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03520712
Recruitment Status : Recruiting
First Posted : May 11, 2018
Last Update Posted : October 14, 2022
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hemophilia A Gene Therapy Clotting Disorders Blood Disorder Biological: Valoctocogene Roxaparvovec Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 3, 2018
Estimated Primary Completion Date : November 2027
Estimated Study Completion Date : November 2027

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: valoctocogene roxaparvovec Open Label
Single administration of BMN270 at a dose of 6E13 vg/kg
Biological: Valoctocogene Roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Other Name: BMN 270

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Efficacy of BMN 270 defined as FVIII activity at or above 5 IU/dL at Week 26. [ Time Frame: 26 weeks ]
  2. Impact of BMN 270 on usage of exogenous FVIII replacement therapy. [ Time Frame: 61 months ]
  3. Impact of BMN 270 on the number of bleeding episodes requiring exogenous FVIII therapy. [ Time Frame: 61 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Biological males only.
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520712

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Contact: Trial Specialist 1-800-983-4587 medinfo@bmrn.com

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South Africa
Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center Recruiting
Johannesburg, South Africa
United Kingdom
Royal Free Hospital Recruiting
London, United Kingdom
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: Medical Director, MD BioMarin Pharmaceutical
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT03520712    
Other Study ID Numbers: BMN 270-203
2017-000662-29 ( EudraCT Number )
First Posted: May 11, 2018    Key Record Dates
Last Update Posted: October 14, 2022
Last Verified: October 2022

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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
Keywords provided by BioMarin Pharmaceutical:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
AAV5 antibodies
Additional relevant MeSH terms:
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Hemostatic Disorders
Hemophilia A
Hematologic Diseases
Blood Coagulation Disorders
Pathologic Processes
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Vascular Diseases
Cardiovascular Diseases