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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03370913
Recruitment Status : Active, not recruiting
First Posted : December 13, 2017
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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 week 52.

Condition or disease Intervention/treatment Phase
Hemophilia A Biological: valoctocogene roxaparvovec Phase 3

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Study Type : Interventional  (Clinical Trial)
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 : December 19, 2017
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

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 Name: BMN 270




Primary Outcome Measures :
  1. Change of the median FVIII activity [ Time Frame: 52 weeks ]

Secondary Outcome Measures :
  1. Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy [ Time Frame: 52 weeks ]
  2. Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 5 years ]


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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 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.

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): NCT03370913


Locations
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United States, California
Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center
Los Angeles, California, United States, 90007-2664
UC Davis Hemophilia Treatment Center
Sacramento, California, United States, 95817
University of California San Diego, Hematology and Oncology, Hemophilia &Thrombosis Treatment Center
San Diego, California, United States, 92122
UCSF Medical Center
San Francisco, California, United States, 94143-0106
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
St. Joseph's Children's Hospital, Center for Bleeding and Clotting Disorders
Tampa, Florida, United States, 33607
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Hematology
Chicago, Illinois, United States, 60611-2605
United States, Kentucky
James Graham Brown Cancer Center
Louisville, Kentucky, United States, 40202
United States, Michigan
University of Michigan, Pediatric Hematology and Oncology
Ann Arbor, Michigan, United States, 48109-5718
Wayne State University, Detroit Medical Center
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine, Department of Pediatrics, Division of Hematology/Oncology
Saint Louis, Missouri, United States, 63110-1093
United States, North Carolina
UNC Hemophilia and Thrombosis Center
Chapel Hill, North Carolina, United States, 27517
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Australia
The Royal Adelaide Hospital (RAH)
Adelaide, Australia
Royal Brisbane and Women's Hospital
Brisbane, Australia
Alfred Hospital
Melbourne, Australia
Fiona Stanley Hospital
Perth, Australia
Royal Prince Alfred Hospital
Sydney, Australia
Belgium
University Hospital Leuven
Leuven, Belgium
Brazil
Campinas Estadual University (UNICAMP) / Campinas Hemocentro / Hematologia E Hemoterapia Center
Campinas, Brazil
Parana's Hematology And Hemotherapy Center (HEMEPAR)
Curitiba, Brazil
Arthur De Siqueira Cavalcanti Hematology State Institute
Rio De Janeiro, Brazil
Sao Paulo University Clinical Hospital
São Paulo, Brazil
Holy Spirit Hematology and Hemotherapy Center
Vitória, Brazil
France
Regional University Hospital of Lille (CHRU de Lille)
Lille, France
Hopital de la Timone Marseille - Assistance Publique des Hopitaux de Marseille
Marseille, France
Germany
Vivantes Clinic im Friedrichshain- Landsberger Allee
Berlin, Germany
University Clinic Bonn
Bonn, Germany
Israel
Chaim Sheba Medical Center
Ramat Gan, Israel
Italy
Maggiore Polyclinic Hospital, IRCCS Ca' Granda, Center for Hemophilia and Thrombosis Angelo Bianchi Bonomi
Milan, Italy
Korea, Republic of
Department of Pediatrics, Kyung Hee University Hospital at Gangdong
Seoul, Korea, Republic of
South Africa
Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center
Johannesburg, South Africa
Spain
Hospital Teresa Herrera
A Coruna, Spain
University Hospital Virgen del Rocio (HUVR)
Seville, Spain
Taiwan
Changhua Christian Hospital
Changhua, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Tri-Service General Hospital
Taipei, Taiwan
United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom
Glasgow Royal Infirmary, Department of Hematology
Glasgow, United Kingdom
Barts and The London School of Medicine and Dentistry, Haemophilia Centre
London, United Kingdom
Hammersmith
London, United Kingdom
St Thomas' Hospital
London, United Kingdom
Churchill Hospital, Oxford Hemophilia and Thrombosis Center
Oxford, United Kingdom
University Hospital Southampton NHS Foundation Trust
Southampton, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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Study Director: Medical Monitor, MD BioMarin Pharmaceutical
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT03370913    
Other Study ID Numbers: BMN 270-301
2017-003215-19 ( EudraCT Number )
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021

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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:
Factor VIII
Gene Therapy
Clotting Disorders
Blood Disorder
Blood Coagulation Disorders
Inherited Blood Coagulation disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases
Inborn
Coagulants
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