Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5 (GENEr8-AAV5+)
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. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03520712 |
Recruitment Status :
Active, not recruiting
First Posted : May 11, 2018
Last Update Posted : April 24, 2024
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Condition or disease | Intervention/treatment | Phase |
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Hemophilia A Gene Therapy Clotting Disorders Blood Disorder | Biological: Valoctocogene Roxaparvovec | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 3 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 2024 |
Estimated Study Completion Date : | November 2024 |
Arm | Intervention/treatment |
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Experimental: valoctocogene roxaparvovec Open Label
Single administration of BMN270 at a dose of 6E13 vg/kg
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Biological: Valoctocogene Roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Other Name: BMN 270 |
- 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 ]
- Efficacy of BMN 270 defined as FVIII activity at or above 5 IU/dL at Week 26. [ Time Frame: 26 weeks ]
- Impact of BMN 270 on usage of exogenous FVIII replacement therapy. [ Time Frame: 61 months ]
- Impact of BMN 270 on the number of bleeding episodes requiring exogenous FVIII therapy. [ Time Frame: 61 months ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
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:
- 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.
Exclusion Criteria:
- 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.
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
Korea, Republic of | |
Kyung Hee University Hospital at Gangdong | |
Seoul, Korea, Republic of | |
Severance Hospital, Yonsei University Health System | |
Seoul, Korea, Republic of | |
South Africa | |
Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center | |
Johannesburg, South Africa | |
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, Taiwan | |
United Kingdom | |
Royal Free Hospital | |
London, United Kingdom | |
University Hospital Southampton NHS Foundation Trust | |
Southampton, United Kingdom |
Study Director: | Medical Director, MD | BioMarin Pharmaceutical |
Responsible Party: | BioMarin Pharmaceutical |
ClinicalTrials.gov Identifier: | NCT03520712 |
Other Study ID Numbers: |
270-203 2017-000662-29 ( EudraCT Number ) |
First Posted: | May 11, 2018 Key Record Dates |
Last Update Posted: | April 24, 2024 |
Last Verified: | April 2024 |
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 |
Hemophilia A Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Coagulation Protein Disorders |
Hemorrhagic Disorders Genetic Diseases, Inborn Factor VIII Coagulants AAV5 antibodies |
Hemostatic Disorders Hemophilia A Hematologic Diseases Blood Coagulation Disorders Blood Coagulation Disorders, Inherited |
Coagulation Protein Disorders Hemorrhagic Disorders Genetic Diseases, Inborn Vascular Diseases Cardiovascular Diseases |