Brief Title
Gene Therapy Study in Severe Haemophilia A Patients (270-201)
Official Title
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
Brief Summary
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 Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
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.
Secondary Outcome
To describe the immune response to the FVIII transgene product and AAV capsid proteins following systemic administration of AAV5-hFVIII-SQ
Condition
Severe Haemophilia A
Intervention
valoctocogene roxaparvovec
Study Arms / Comparison Groups
valoctocogene roxaparvovec
Description: Single administration of valoctocogene roxaparvovec at escalating doses.
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
15
Start Date
August 2015
Completion Date
March 2024
Primary Completion Date
March 2024
Eligibility Criteria
Inclusion Criteria:
1. Males 18 years or older with established severe Haemophilia A (endogenous FVIII level
≤1 IU/dL) as evidenced by their medical history.
2. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure
days (EDs)
3. 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
4. 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
5. Sexually active patients must be willing to use an acceptable method of contraception.
Exclusion Criteria:
1. Detectable pre-existing immunity to the AAV5 capsid as measured by AAV5 transduction
inhibition or AAV5 total antibodies
2. Any evidence of immunosuppressive disorder or active chronic infection including
hepatis B, hepatitis C, HIV
3. 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
4. Evidence of any bleeding disorder not related to haemophilia A
5. 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
6. 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.
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Director, MD, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT02576795
Organization ID
BMN 270-201
Secondary IDs
2014-003880-38
Responsible Party
Sponsor
Study Sponsor
BioMarin Pharmaceutical
Study Sponsor
Medical Director, MD, Study Director, BioMarin Pharmaceutical
Verification Date
January 2021