Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors

January 3, 2023 updated by: BioMarin Pharmaceutical

A Phase 1/2 Safety, Tolerability, and Efficacy Study of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Active or Prior Inhibitors

This Phase I/II clinical study will evaluate the safety and efficacy of valoctocogene roxaparvovec in patients with severe haemophilia A and inhibitors to FVIII. Part A of the study will involve subjects who have active inhibitors to FVIII, and Part B involving subjects with a prior history of inhibitors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

20

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 Contact

Study Locations

  • Brazil
      • Campinas, Brazil
        • Recruiting
        • Hemocentro da UNICAMP
  • Italy
      • Milan, Italy
        • Recruiting
        • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Recruiting
        • Kyung Hee University Hospital at Gangdong
  • Taiwan
      • Kaohsiung, Taiwan
        • Recruiting
        • Kaohsiung Medical University - Chung-Ho Memorial Hospital
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital
  • United Kingdom
      • Birmingham, United Kingdom
        • Recruiting
        • Queen Elizabeth Hospital
      • London, United Kingdom
        • Recruiting
        • Royal Free Hospital
      • London, United Kingdom
        • Recruiting
        • Guy's and St Thomas' NHS Foundation Trust
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles
      • Sacramento, California, United States, 95817
        • Recruiting
        • UC Davis Hemophilia Treatment Center

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

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Males ≥ 18 years of age with hemophilia A and documented prior residual FVIII activity ≤ 1 IU/dL including, but not limited to, at the time of detected inhibitors, at the time of signing the informed consent.

  2. History of a positive inhibitor result with the first positive result at least 12 month prior to Screening.

    Part A: Demonstrated no immunological tolerance to exogenous FVIII. Part B: Demonstrated tolerance to exogenous FVIII and negative FVIII inhibitor screening titer < 0.6 BU.

  3. Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor & hemophilia therapy Hx over previous 12 months.
  4. Sexually active participants must agree to use an acceptable method of effective contraception. Participants must agree to contraception use for at least 12 weeks post-infusion.
  5. Willing to abstain from consumption of alcohol for at least the first 52 weeks following BMN 270 infusion.

Exclusion Criteria:

  1. Detectable pre-existing antibodies to the AAV5 capsid.
  2. Any evidence of active infection or any immunosuppressive disorder; patients with HIV infection and undetectable viral load are not excluded.
  3. Currently undergoing, or plan to receive during the study, immune tolerance induction therapy or prophylaxis with FVIII (Part A only).
  4. Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy.
  5. Evidence of any bleeding disorder not related to hemophilia A.

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 Open Label
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg in Active Inhibitor Population (Part A) and Prior Inhibitor Population (Part B).
Biological: Valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Other Names:
  • BMN 270

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with treatment-related adverse events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 after administration of BMN 270.
Time Frame: 60 months
60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of the median Factor VIII activity.
Time Frame: 60 months
Changes in the median Factor VIII activity (IU/mL) after administration of BMN 270 which will be measured using the chromogenic FVIII assay.
60 months
A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270.
Time Frame: 60 months
FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
60 months
Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270.
Time Frame: 60 months
FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
60 months
Change in the annualized utilization of hemophilia therapy after administration of BMN 270
Time Frame: 60 months
60 months
Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270.
Time Frame: 60 months
60 months

Collaborators and Investigators

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

Sponsor

BioMarin Pharmaceutical

Investigators

  • Study Director: Medical Monitor, MD, BioMarin Pharmaceutical

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)

December 10, 2020

Primary Completion (Anticipated)

February 1, 2029

Study Completion (Anticipated)

February 1, 2029

Study Registration Dates

First Submitted

November 30, 2020

First Submitted That Met QC Criteria

December 24, 2020

First Posted (Actual)

December 28, 2020

Study Record Updates

Last Update Posted (Actual)

January 4, 2023

Last Update Submitted That Met QC Criteria

January 3, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BMN 270-205
  • 2019-003213-34 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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