Brief Title
Gene Therapy Study in Severe Haemophilia A Patients
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
BMN 270
Study Arms / Comparison Groups
BMN 270
Description: BMN 270 is administered as a single IV Infusion.
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
Genetic
Estimated Enrollment
15
Start Date
August 2015
Completion Date
March 2024
Primary Completion Date
March 2024
Eligibility Criteria
Inclusion Criteria:
1. 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 base FVIII level
is 1 IU/dL or less
2. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure
days (EDs)
3. Greater or equal to 12 bleeding episodes only if on on-demand therapy over the
previous 12 months. Does not apply to patients on prophylaxis
4. Able to sign informed consent and comply with requirements of the trial
5. 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
6. 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. After 6 months, subjects may stop contraception use only if they have
had 3 consecutive semen samples below the limit of detection of the test.
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 active infection or any immunosuppressive disorder.
3. HIV positive
4. Significant liver dysfunction as defined by abnormal elevation of:
- ALT (alanine transaminase) to 3 times the upper limit of normal;
- Bilirubin above 3 times the upper limit of normal;
- Alkaline phosphatase above 3 times the upper limit of normal; or
- INR (international normalized ratio) ≥ 1.4.
5. 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.
6. Evidence of any bleeding disorder not related to Haemophilia A
7. Platelet count of < 100 x 10^9/L
8. Creatinine ≥ 1.5 mg/dL
9. Liver cirrhosis of any etiology as assessed by liver ultrasound
10. Hepatitis B if surface antigen is positive
11. Hepatitis C if RNA is positive
12. Treatment with any IP within 30 days prior to the end of the screening period
13. Any disease or condition at the physician's discretion that 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.
14. Prior treatment with any gene transfer agent
15. Major surgery planned in the 16-week period following the viral infusion
16. Use of systemic immunosuppressive agents or live vaccines within 30 days before 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
BMN270-201
Secondary IDs
2014-003880-38
Responsible Party
Sponsor
Study Sponsor
BioMarin Pharmaceutical
Study Sponsor
Medical Director, MD, Study Director, BioMarin Pharmaceutical
Verification Date
July 2020