Working… Menu

Gene Therapy Study in Severe Haemophilia A Patients (270-201)

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. Identifier: NCT02576795
Recruitment Status : Active, not recruiting
First Posted : October 15, 2015
Last Update Posted : January 22, 2021
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE October 5, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date January 22, 2021
Study Start Date  ICMJE August 2015
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2020)
  • 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 ]
  • 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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
  • Number of treatment related adverse events as assessed by laboratory assessments and vital signs [ Time Frame: 61 Months ]
  • Number of participants that express FVIII per protocol as assessed by the FVIII activity assays [ Time Frame: 61 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2020)
  • 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 ]
  • Frequency of FVIII replacement therapy during the study [ Time Frame: 85 Months ]
  • Number of bleeding episodes requiring treatment during the study [ Time Frame: 85 Months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
  • Number of Participants that show an immune response following administration of BMN 270 as assessed by cytotoxic T lymphocytes reaction per protocol after the administration of BMN 270 [ Time Frame: 61 Months ]
  • Frequency of administration of FVIII replacement therapy after administration of BMN 270 [ Time Frame: 61 Months ]
  • Number of bleeding episodes requiring treatment after the administration of BMN 270 [ Time Frame: 61 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Gene Therapy Study in Severe Haemophilia A Patients (270-201)
Official Title  ICMJE 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Severe Haemophilia A
Intervention  ICMJE Biological: valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A
Other Name: BMN 270
Study Arms  ICMJE Experimental: valoctocogene roxaparvovec
Single administration of valoctocogene roxaparvovec at escalating doses.
Intervention: Biological: valoctocogene roxaparvovec
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 7, 2016)
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2015)
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Biological males only
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02576795
Other Study ID Numbers  ICMJE BMN 270-201
2014-003880-38 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BioMarin Pharmaceutical
Study Sponsor  ICMJE BioMarin Pharmaceutical
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director, MD BioMarin Pharmaceutical
PRS Account BioMarin Pharmaceutical
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP