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Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)

Sponsor
BioMarin Pharmaceutical (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03370913
Collaborator
(none)
134
Enrollment
48
Locations
1
Arm
82.4
Anticipated Duration (Months)
2.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase III clinical study will assess the efficacy of BMN 270 defined as FVIII activity, during weeks 49-52 following intravenous infusion of BMN 270 and assess the impact of BMN 270 on usage of exogenous FVIII replacement therapy and the number of bleeding episodes from week 5 to last visit by data cutoff.

Condition or Disease Intervention/Treatment Phase
  • Biological: valoctocogene roxaparvovec
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
134 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions
Actual Study Start Date :
Dec 19, 2017
Actual Primary Completion Date :
Nov 16, 2020
Anticipated Study Completion Date :
Nov 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: valoctocogene roxaparvovec Open Label

Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg

Biological: valoctocogene roxaparvovec
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Other Names:
  • BMN 270

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change from baseline in the median FVIII activity, as measured by chromogenic substrate assay, during Weeks 49-52 post-BMN 270 infusion [52 weeks]

    Secondary Outcome Measures

    1. Change from baseline in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy from Week 5 to last visit by data cut-off [52 weeks]

    2. Change from baseline in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment from Week 5 to last visit by data cut-off [52 weeks]

    Other Outcome Measures

    1. Percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.03 in the first 52 weeks following valoctocogene roxaparvovec infusion [52 weeks]

    2. Percentage of participants with treatment-related adverse events, as assessed by de novo development of FVIII inhibitors in the first 52 weeks following valoctocogene roxaparvovec infusion [52 weeks]

    3. Percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.03 during years 2-5 following valoctocogene roxaparvovec infusion [5 years]

    4. Percentage of participants with treatment-related adverse events, as assessed by de novo development of FVIII inhibitors during years 2-5 following valoctocogene roxaparvovec infusion [5 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Males ≥ 18 years of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as evidenced by medical history, at the time of signing the informed consent.

    2. Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry.

    3. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).

    4. No previous documented history of a detectable FVIII inhibitor, and results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least one week apart within the past 12 months.

    Exclusion Criteria:

    1. Detectable pre-existing antibodies to the AAV5 capsid.

    2. Any evidence of active infection or any immunosuppressive disorder, including HIV infection.

    3. Significant liver dysfunction.

    4. Prior liver biopsy showing significant fibrosis.

    5. Evidence of any bleeding disorder not related to hemophilia A.

    6. Platelet count of < 100 x 10^9/L.

    7. Creatinine ≥ 1.5 mg/dL.

    8. Liver cirrhosis of any etiology as assessed by liver ultrasound.

    9. Chronic or active hepatitis B.

    10. Active Hepatitis C.

    11. Active malignancy, except non-melanoma skin cancer.

    12. History of hepatic malignancy.

    13. History of arterial or venous thromboembolic events.

    14. Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center Los Angeles California United States 90007-2664
    2 UC Davis Hemophilia Treatment Center Sacramento California United States 95817
    3 University of California San Diego, Hematology and Oncology, Hemophilia &Thrombosis Treatment Center San Diego California United States 92122
    4 UCSF Medical Center San Francisco California United States 94143-0106
    5 University of Colorado Aurora Colorado United States 80045
    6 St. Joseph's Children's Hospital, Center for Bleeding and Clotting Disorders Tampa Florida United States 33607
    7 Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Hematology Chicago Illinois United States 60611-2605
    8 James Graham Brown Cancer Center Louisville Kentucky United States 40202
    9 University of Michigan, Pediatric Hematology and Oncology Ann Arbor Michigan United States 48109-5718
    10 Wayne State University, Detroit Medical Center Detroit Michigan United States 48201
    11 University of Minnesota Minneapolis Minnesota United States 55455
    12 Washington University School of Medicine, Department of Pediatrics, Division of Hematology/Oncology Saint Louis Missouri United States 63110-1093
    13 UNC Hemophilia and Thrombosis Center Chapel Hill North Carolina United States 27517
    14 Nationwide Children's Hospital Columbus Ohio United States 43205
    15 The Royal Adelaide Hospital (RAH) Adelaide Australia
    16 Royal Brisbane and Women's Hospital Brisbane Australia
    17 Alfred Hospital Melbourne Australia
    18 Fiona Stanley Hospital Perth Australia
    19 Royal Prince Alfred Hospital Sydney Australia
    20 University Hospital Leuven Leuven Belgium
    21 Campinas Estadual University (UNICAMP) / Campinas Hemocentro / Hematologia E Hemoterapia Center Campinas Brazil
    22 Parana's Hematology And Hemotherapy Center (HEMEPAR) Curitiba Brazil
    23 Arthur De Siqueira Cavalcanti Hematology State Institute Rio De Janeiro Brazil
    24 Sao Paulo University Clinical Hospital São Paulo Brazil
    25 Holy Spirit Hematology and Hemotherapy Center Vitória Brazil
    26 Regional University Hospital of Lille (CHRU de Lille) Lille France
    27 Hopital de la Timone Marseille - Assistance Publique des Hopitaux de Marseille Marseille France
    28 Vivantes Clinic im Friedrichshain- Landsberger Allee Berlin Germany
    29 University Clinic Bonn Bonn Germany
    30 Chaim Sheba Medical Center Ramat Gan Israel
    31 Maggiore Polyclinic Hospital, IRCCS Ca' Granda, Center for Hemophilia and Thrombosis Angelo Bianchi Bonomi Milan Italy
    32 Department of Pediatrics, Kyung Hee University Hospital at Gangdong Seoul Korea, Republic of
    33 Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center Johannesburg South Africa
    34 Hospital Teresa Herrera A Coruna Spain
    35 University Hospital Virgen del Rocio (HUVR) Seville Spain
    36 Changhua Christian Hospital Changhua Taiwan
    37 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan
    38 Taichung Veterans General Hospital Taichung Taiwan
    39 National Taiwan University Hospital Taipei Taiwan
    40 Tri-Service General Hospital Taipei Taiwan
    41 Queen Elizabeth Hospital Birmingham United Kingdom
    42 Addenbrookes Hospital Cambridge United Kingdom
    43 Glasgow Royal Infirmary, Department of Hematology Glasgow United Kingdom
    44 Barts and The London School of Medicine and Dentistry, Haemophilia Centre London United Kingdom
    45 Hammersmith London United Kingdom
    46 St Thomas' Hospital London United Kingdom
    47 Churchill Hospital, Oxford Hemophilia and Thrombosis Center Oxford United Kingdom
    48 University Hospital Southampton NHS Foundation Trust Southampton United Kingdom

    Sponsors and Collaborators

    • BioMarin Pharmaceutical

    Investigators

    • Study Director: Medical Monitor, MD, BioMarin Pharmaceutical

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    BioMarin Pharmaceutical
    ClinicalTrials.gov Identifier:
    NCT03370913
    Other Study ID Numbers:
    • BMN 270-301
    • 2017-003215-19
    First Posted:
    Dec 13, 2017
    Last Update Posted:
    Aug 3, 2022
    Last Verified:
    Aug 1, 2022
    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
    Inborn
    Factor VIII
    Coagulants
    Additional relevant MeSH terms:
    Hemophilia A

    Study Results

    No Results Posted as of Aug 3, 2022