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

Hemophilia A Clinical Trial

— GENEr8-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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03520712
• Other study ID #: 270-203
• Secondary ID: 2017-000662-29
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 3, 2018
• Est. completion date: November 2024

Study information

• Verified date: April 2024
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 3
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Blood Disorder
• Clotting Disorders
• Gene Therapy
• Hematologic Diseases
• Hemophilia A
• Hemostatic Disorders

Intervention

Biological:
• Valoctocogene Roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A

Locations

Country	Name	City	State
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
South Africa	Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center	Johannesburg
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
United Kingdom	Royal Free Hospital	London
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

Korea, Republic of,  South Africa,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Efficacy of BMN 270 defined as FVIII activity at or above 5 IU/dL at Week 26.		26 weeks
Secondary	Impact of BMN 270 on usage of exogenous FVIII replacement therapy.		61 months
Secondary	Impact of BMN 270 on the number of bleeding episodes requiring exogenous FVIII therapy.		61 months