A Phase 1/2 study to evaluate the safety and efficacy of BMN 270 gene therapy in patients with severe Haemophilia A

Phase 1

• Conditions: Haemophilia A; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2014-003880-38-GB
• Lead Sponsor: BioMarin Pharmaceutical Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-09
• Last Update Posted: 6 July 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 15

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 receiving 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) on 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 vector or 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified