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Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors (GENEr8-INH)

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ClinicalTrials.gov Identifier: NCT04684940
Recruitment Status : Recruiting
First Posted : December 28, 2020
Last Update Posted : April 24, 2024
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hemophilia A With Inhibitor Hemophilia A With Anti Factor VIII Biological: Valoctocogene roxaparvovec Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 10, 2020
Estimated Primary Completion Date : February 2029
Estimated Study Completion Date : February 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arms and Interventions
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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 Name: BMN 270 (GENEr8)


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Change in the annualized utilization of hemophilia therapy after administration of BMN 270 [ Time Frame: 60 months ]
  5. Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270. [ Time Frame: 60 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Biological males only
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04684940


Contacts
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Contact: Trial Specialist 1-800-983-4587 medinfo@bmrn.com

Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
UC Davis Hemophilia Treatment Center Recruiting
Sacramento, California, United States, 95817
Brazil
Hemocentro Da UNICAMP Recruiting
Campinas, Brazil
Germany
University Hospital Bonn, Institute of Experimental Hematology and Transfusion Medicine Recruiting
Bonn, Germany
Israel
Chaim Sheba Medical Center Recruiting
Ramat Gan, Israel
Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Recruiting
Milan, Italy
Korea, Republic of
Kyung Hee University Hospital at Gangdong Recruiting
Seoul, Korea, Republic of
Severance Hospital Yonsei University Recruiting
Seoul, Korea, Republic of
South Africa
Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center Recruiting
Johannesburg, South Africa
Taiwan
Kaohsiung Medical University - Chung-Ho Memorial Hospital Recruiting
Kaohsiung, Taiwan
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan
United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom
Guy's and St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom
Royal Free Hospital Recruiting
London, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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Study Director: Medical Monitor, MD BioMarin Pharmaceutical
More Information
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT04684940    
Other Study ID Numbers: 270-205
2019-003213-34 ( EudraCT Number )
First Posted: December 28, 2020    Key Record Dates
Last Update Posted: April 24, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioMarin Pharmaceutical:
Gene Therapy
Clotting Disorders
Blood Disorder
Blood Coagulation Disorders
Inherited Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
 Hemorrhagic Disorders
Genetic DIseases
Factor VIII
Coagulants
Hemophilia A
AAV5 vector
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
 Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn