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

Phase 1

Completed

• Conditions: Severe Haemophilia A
• Interventions: Biological: valoctocogene roxaparvovec

• Registration Number: NCT02576795
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-09-28
• Study First Submitted: 2015-10-05
• Study First Submitted QC: 2015-10-13
• Study First Posted: 2015-10-15
• Primary Completion: 2024-02-14
• Study Completion: 2024-02-14
• Results First Submitted: 2025-02-12
• Status Verified: 2025-03
• Results First Submitted QC: 2025-03-24
• Last Update Submitted: 2025-03-24
• Results First Posted: 2025-04-10
• Last Update Posted: 2025-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

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 adeno-associated virus 5 (AAV5) transduction inhibition (TI) 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
valoctocogene roxaparvovec	valoctocogene roxaparvovec	Single administration of valoctocogene roxaparvovec at escalating doses.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events	Approximately up to 7 years after dosing	Adverse events (AEs) with onset or worsening after the investigational product were included. Participants with more than one AE of the same category were counted only once for that category.; Serious adverse event (SAE)
Number of Participant With Median FVIII Activity Levels >= 5 IU/dL Using Chromogenic Substrate Assay (CSA)	Week 13-16 post-BMN 270 infusion	Responder/Non responder status, where a responder was defined as a participant with median FVIII activity of \>= 5 IU/dL during Week 13-16 post-BMN 270 infusion
Median FVIII Activity as Measured by Chromogenic Substrate Assay During Week 13-16 Post-BMN 270 Infusion	Week 13-16 post-BMN 270 infusion	Values for FVIII activity were excluded from analysis if obtained within 72 hours since the last infusion of exogenous FVIII replacement therapy; FVIII activity levels below the Lower limit of quantitation (LLOQ) will be imputed with 0 IU/dL; Q1: 25% Percentile; Q3: 75% Percentile

Secondary Outcome Measures

Name	Time	Method
Annualized Factor VIII Utilization During Week 5 and Beyond	Week 5 and Beyond (Approximately 7 years post Infusion)	Annualized FVIII use (IU/kg/yr.) =\[Sum of FVIII use (IU/kg) during calculation period\] / \[Total number of days during the calculation period\] ×365.25
Annualized Factor VIII Infusion Rate During Week 5 and Beyond	Week 5 and Beyond (Approximately 7 years post Infusion)	Annualized FVIII infusion rate (count/yr.) = \[Number of FVIII replacement infusions during calculation period\] / \[Total number of days during the calculation period\] ×365.25
Annualized Bleeding Rate Requiring Exogenous Factor VIII Replacement Treatment During Week 5 and Beyond	Week 5 and Beyond (Approximately 7 years post Infusion)	ABR= \[Number of bleeding episodes during calculation period\] / \[Total number of days during the calculation period\] ×365.25; A bleeding episode (treated) was defined as a bleed or symptoms associated with the development of a bleed (or multiple bleeds occurring in the same day) requiring FVIII replacement treatment within 72 hours of the start of the bleed.; The baseline values for the secondary efficacy endpoints were based on the historical data prior to study enrollment.; Annualized bleeding rate (ABR)

Trial Locations

Locations (5)

Queen Elizabeth Hospital Birmingham; 🇬🇧 Birmingham, United Kingdom

Addenbrooke's Hospital; 🇬🇧 Cambridge, United Kingdom

St. Thomas' Hospital; 🇬🇧 London, United Kingdom

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, United Kingdom

The Royal London Hospital; 🇬🇧 London, United Kingdom