- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02576795
Gene Therapy Study in Severe Haemophilia A Patients (270-201)
December 14, 2023 updated by: BioMarin Pharmaceutical
A Phase 1/2, Dose-Escalation, Safety, Tolerability and Efficacy Study of Valoctocogene Roxaparvovec, an Adenovirus-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Patients With Severe Haemophilia A
This study is being conducted by BioMarin Pharmaceutical Inc. as an open label, dose escalation study in order to determine the safety and efficacy of valoctocogene roxaparvovec (an Adenovirus-Associated Virus based gene therapy vector in participants with severe haemophilia A.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Birmingham, United Kingdom
- Queen Elizabeth Hospital Birmingham
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Cambridge, United Kingdom
- Addenbrooke's Hospital
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London, United Kingdom
- The Royal London Hospital
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London, United Kingdom
- St. Thomas' Hospital
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Southampton, United Kingdom
- University Hospital Southampton NHS Foundation Trust
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Males 18 years or older with established severe Haemophilia A (endogenous FVIII level ≤1 IU/dL) as evidenced by their medical history.
- Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs)
- Greater than or equal to 12 bleeding episodes for patients on on-demand FVIII replacement therapy over the previous 12 months. Does not apply to patients on prophylaxis
- No history of inhibitor, and results from a modified Nijmegen Bethesda assay of less than 0.6 Bethesda Units (BU) 2 consecutive occasions at least one week apart within the past 12 months
- Sexually active patients must be willing to use an acceptable method of contraception.
Exclusion Criteria:
- Detectable pre-existing immunity to the AAV5 capsid as measured by AAV5 transduction inhibition or AAV5 total antibodies
- Any evidence of immunosuppressive disorder or active chronic infection including hepatis B, hepatitis C, HIV
- Significant liver dysfunction as defined by abnormal elevation ofliver function tests, or for patients who have undergone liver imaging or biopsy and found to have evidence of grade 3 or higher fibrosis
- Evidence of any bleeding disorder not related to haemophilia A
- 12. Treatment with any investigational product within 30 days prior to the end of the screening period, or any previous exposure to any gene transfer therapy
- Any disease or condition that per the physician's discretion would prevent the patient from fully complying with the requirements of the study including possible corticosteroid treatment outlined in the protocol. The physician may exclude patients unwilling or unable to agree on not using alcohol for the 16-week period following the viral infusion.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: valoctocogene roxaparvovec
Single administration of valoctocogene roxaparvovec at escalating doses.
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Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with treatment-related adverse events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for 7 years following valoctocogene roxaparvovec infusion.
Time Frame: 85 Months
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85 Months
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To determine the dose of AAV5-hFVIII-SQ required to achieve expression of FVIII at or above 5% of normal activity (>5 IU/dL) at 16 weeks after infusion.
Time Frame: 85 Months
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The kinetics, duration and magnitude of AAV-mediated FVIII activity in individuals with haemophilia A will be determined and correlated to an appropriate BMN 270 dose.
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85 Months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To describe the immune response to the FVIII transgene product and AAV capsid proteins following systemic administration of AAV5-hFVIII-SQ
Time Frame: 85 Months
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85 Months
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Frequency of FVIII replacement therapy during the study
Time Frame: 85 Months
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85 Months
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Number of bleeding episodes requiring treatment during the study
Time Frame: 85 Months
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85 Months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Director, MD, BioMarin Pharmaceutical
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Quinn J, Delaney KA, Wong WY, Miesbach W, Bullinger M. Psychometric Validation of the Haemo-QOL-A in Participants with Hemophilia A Treated with Gene Therapy. Patient Relat Outcome Meas. 2022 Jul 18;13:169-180. doi: 10.2147/PROM.S357555. eCollection 2022.
- Rosen S, Tiefenbacher S, Robinson M, Huang M, Srimani J, Mackenzie D, Christianson T, Pasi KJ, Rangarajan S, Symington E, Giermasz A, Pierce GF, Kim B, Zoog SJ, Vettermann C. Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy. Blood. 2020 Nov 26;136(22):2524-2534. doi: 10.1182/blood.2020005683.
- Fong S, Yates B, Sihn CR, Mattis AN, Mitchell N, Liu S, Russell CB, Kim B, Lawal A, Rangarajan S, Lester W, Bunting S, Pierce GF, Pasi KJ, Wong WY. Interindividual variability in transgene mRNA and protein production following adeno-associated virus gene therapy for hemophilia A. Nat Med. 2022 Apr;28(4):789-797. doi: 10.1038/s41591-022-01751-0. Epub 2022 Apr 11.
- Pasi KJ, Laffan M, Rangarajan S, Robinson TM, Mitchell N, Lester W, Symington E, Madan B, Yang X, Kim B, Pierce GF, Wong WY. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 2021 Nov;27(6):947-956. doi: 10.1111/hae.14391. Epub 2021 Aug 11.
- Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, Laffan M, Russell CB, Li M, Pierce GF, Wong WY. Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A. N Engl J Med. 2020 Jan 2;382(1):29-40. doi: 10.1056/NEJMoa1908490.
- Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, Yu H, Vettermann C, Pierce GF, Wong WY, Pasi KJ. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017 Dec 28;377(26):2519-2530. doi: 10.1056/NEJMoa1708483. Epub 2017 Dec 9.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2015
Primary Completion (Estimated)
March 1, 2024
Study Completion (Estimated)
March 1, 2024
Study Registration Dates
First Submitted
October 5, 2015
First Submitted That Met QC Criteria
October 13, 2015
First Posted (Estimated)
October 15, 2015
Study Record Updates
Last Update Posted (Actual)
December 15, 2023
Last Update Submitted That Met QC Criteria
December 14, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BMN 270-201
- 2014-003880-38 (EudraCT Number)
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Clinical Trials on valoctocogene roxaparvovec
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