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

Severe Haemophilia A Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02576795
• Other study ID #: BMN 270-201
• Secondary ID: 2014-003880-38
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 2015
• Est. completion date: March 2024

Study information

• Verified date: December 2023
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Severe Haemophilia A

Intervention

Biological:
• valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		85 Months
Primary	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.	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.	85 Months
Secondary	To describe the immune response to the FVIII transgene product and AAV capsid proteins following systemic administration of AAV5-hFVIII-SQ		85 Months
Secondary	Frequency of FVIII replacement therapy during the study		85 Months
Secondary	Number of bleeding episodes requiring treatment during the study		85 Months