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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 : October 14, 2022
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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.

Condition or disease Intervention/treatment Phase
Severe Haemophilia A Biological: valoctocogene roxaparvovec Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : August 2015
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: valoctocogene roxaparvovec
Single administration of valoctocogene roxaparvovec at escalating doses.
Biological: valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A
Other Name: BMN 270

Primary Outcome Measures :
  1. 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 ]
  2. 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.

Secondary Outcome Measures :
  1. 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 ]
  2. Frequency of FVIII replacement therapy during the study [ Time Frame: 85 Months ]
  3. Number of bleeding episodes requiring treatment during the study [ Time Frame: 85 Months ]

Information from the National Library of Medicine

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.

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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:

  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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT02576795

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United Kingdom
Queen Elizabeth Hospital Birmingham
Birmingham, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
St. Thomas' Hospital
London, United Kingdom
The Royal London Hospital
London, United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: Medical Director, MD BioMarin Pharmaceutical
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: BioMarin Pharmaceutical Identifier: NCT02576795    
Other Study ID Numbers: BMN 270-201
2014-003880-38 ( EudraCT Number )
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: October 14, 2022
Last Verified: October 2022

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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
Keywords provided by BioMarin Pharmaceutical:
Haemophilia A
Gene Therapy
Clotting Disorders
Blood Disorder
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
AAV5 vector
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn