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

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

Start Date

April 3, 2018

Completion Date

November 2027

Primary Completion Date

November 2027

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.

Gender

Male

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Medical Director, MD, 1-800-983-4587, [email protected]

Location Countries

South Africa

Location Countries

South Africa

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

February 2022