Working... Menu

Gene Therapy Study in Severe Haemophilia A Patients

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 : April 11, 2018
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 BMN 270 (an Adenovirus-Associated Virus based gene therapy vector in participants with severe Haemophilia A.

Condition or disease Intervention/treatment Phase
Severe Haemophilia A Genetic: BMN 270 Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
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 BMN 270, 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 : February 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BMN 270
BMN 270 is administered as a single IV Infusion.
Genetic: BMN 270

Primary Outcome Measures :
  1. Number of treatment related adverse events as assessed by laboratory assessments and vital signs [ Time Frame: 61 Months ]
  2. Number of participants that express FVIII per protocol as assessed by the FVIII activity assays [ Time Frame: 61 Months ]

Secondary Outcome Measures :
  1. 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 ]
  2. Frequency of administration of FVIII replacement therapy after administration of BMN 270 [ Time Frame: 61 Months ]
  3. Number of bleeding episodes requiring treatment after the administration of BMN 270 [ Time Frame: 61 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.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males that are 18 years or older with established severe haemophilia A as evidenced by their medical history. Patients will be considered as severe if their FVIII baseline level is 1 IU/dL or less
  • Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs)
  • Greater or equal to 12 bleeding episodes only if receiving on-demand therapy over the previous 12 months. Does not apply to patients on prophylaxis
  • Able to sign informed consent and comply with requirements of the trial
  • No history of inhibitor, or no inhibitor on 2 consecutive occasions within the past 12 months using a modified Nijmegen Bethesda assay higher than 0.6 Bethesda Units (BU)
  • Sexually active patients must be willing to use an acceptable method of contraception such as double barrier, including hormonal contraception for at least 6 months post-treatment.

Exclusion Criteria:

  • Detectable pre-existing immunity to the AAV capsid as measured by AAV transduction inhibition and AAV total antibodies
  • Any evidence of active infection or any immunosuppressive disorder.
  • Patients that are HIV positive are excluded.
  • Significant liver dysfunction as defined by abnormal elevation of ALT (alanine transaminase) to 3 times the upper limit of normal, bilirubin, alkaline phosphatase, or an INR (international normalized ratio) of 1.4.
  • Potential participants who have had a liver biopsy in the past 3 years are excluded if they had significant fibrosis of 3 or 4 as rated on a scale of 0-4.
  • Evidence of any bleeding disorder not related to Haemophilia A
  • Platelet count of < 100 x 10e9/L
  • Creatinine ≥ 1.5 mg/dL
  • Liver cirrhosis of any etiology as assessed by liver ultrasound
  • Hepatitis B if surface antigen is positive
  • Hepatitis C if RNA is positive
  • Treatment with any IP within 30 days prior to the screening visit
  • Any disease or condition at the physician's discretion that would prevent the patient from fully complying with the requirements of the study. The physician may exclude patients unwilling or unable to agree on not using alcohol for the 16-week period following the viral infusion.
  • Receipt of any vector or gene transfer agent.

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

Layout table for location information
United Kingdom
Hampshire Hospitals NHS Foundation Trust
Basingstoke, United Kingdom, RG24 9NA
Queen Elizabeth Hospital Birmingham
Birmingham, United Kingdom, B15 2TH
University Hospitals Bristol NHS Foundation Trust
Bristol, United Kingdom, BS1 3NU
Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom, CB2 0QQ
Greater Glasgow Health Board
Glasgow, United Kingdom, G12 OXH
Barts Health NHS Trust
London, United Kingdom, E1 1BB
Guy's & St. Thomas' NHS Foundation Trust
London, United Kingdom, SE1 7EH
Imperial College Healthcare NHS Trust
London, United Kingdom, W2 1NY
University Hospital Southampton NHS Foundation Trust
Southampton, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: BioMarin Pharmaceutical Identifier: NCT02576795     History of Changes
Other Study ID Numbers: BMN270-201
2014-003880-38 ( EudraCT Number )
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: April 2018

Keywords provided by BioMarin Pharmaceutical:
Haemophilia A
Gene Therapy
Clotting Disorders
Blood Disorder

Additional relevant MeSH terms:
Layout table for MeSH terms
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII