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

March 24, 2025 updated by: BioMarin Pharmaceutical

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Birmingham, United Kingdom
        • Queen Elizabeth Hospital Birmingham
      • Cambridge, United Kingdom
        • Addenbrooke's Hospital
      • London, United Kingdom
        • The Royal London Hospital
      • London, United Kingdom
        • St. Thomas' Hospital
      • Southampton, United Kingdom
        • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: valoctocogene roxaparvovec
Single administration of valoctocogene roxaparvovec at escalating doses.
Biological: valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A
Other Names:
  • BMN 270

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment Emergent Adverse Events
Time Frame: 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)
Approximately up to 7 years after dosing
Number of Participant With Median FVIII Activity Levels >= 5 IU/dL Using Chromogenic Substrate Assay (CSA)
Time Frame: 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
Week 13-16 post-BMN 270 infusion
Median FVIII Activity as Measured by Chromogenic Substrate Assay During Week 13-16 Post-BMN 270 Infusion
Time Frame: 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
Week 13-16 post-BMN 270 infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Bleeding Rate Requiring Exogenous Factor VIII Replacement Treatment During Week 5 and Beyond
Time Frame: 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)
Week 5 and Beyond (Approximately 7 years post Infusion)
Annualized Factor VIII Utilization During Week 5 and Beyond
Time Frame: 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
Week 5 and Beyond (Approximately 7 years post Infusion)
Annualized Factor VIII Infusion Rate During Week 5 and Beyond
Time Frame: 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
Week 5 and Beyond (Approximately 7 years post Infusion)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

BioMarin Pharmaceutical

Investigators

  • Study Director: Medical Director, MD, BioMarin Pharmaceutical

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2015

Primary Completion (Actual)

February 14, 2024

Study Completion (Actual)

February 14, 2024

Study Registration Dates

First Submitted

October 5, 2015

First Submitted That Met QC Criteria

October 13, 2015

First Posted (Estimated)

October 15, 2015

Study Record Updates

Last Update Posted (Actual)

April 10, 2025

Last Update Submitted That Met QC Criteria

March 24, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BMN 270-201
  • 2014-003880-38 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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