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Trial record 19 of 466 for:    Inherited Bleeding Disorder

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03370913
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : November 11, 2019
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Brief Summary:
This clinical trial is being conducted to learn more about a potential treatment (valoctocogene roxaparvovec) for people with severe hemophilia A. This research study will test and confirm the safety and effectiveness of the 6E13 vg/kg dose of the study drug (valoctocogene roxaparvovec) that contains the correct gene to make Factor VIII so that the body can make its own Factor VIII that functions properly. Only one dose of valoctocogene roxaparvovec is being given in this study, and this dose has been previously studied in another clinical trial in patients with hemophilia A. This is a phase 3 study which is meant to show that the study drug is safe and works to help treat hemophilia A. The study will see if liver cells are able to make Factor VIII that functions properly after receiving this study drug. The study will also examine the effects that the study drug has on how much Factor VIII concentrates patients have to inject into their veins and on their bleeding episodes after the study drug has been administered. Finally, the study will see if and how the body responds to the study drug - for example, whether liver cells become inflamed or whether the body makes antibodies (something the immune system makes to protect itself against things like bacteria and viruses) against the vector or the new Factor VIII gene.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
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 : December 2022
Estimated Study Completion Date : September 2023

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. Assess the impact of valoctocogene roxaparvovec following Patient Reported Outcome (PRO) Haemo-QoL-A. [ Time Frame: 52 weeks ]
    Haemo-QoL-A is a hemophilia-specific, health-related quality of life questionnaire for adults

  2. Assess the impact of valoctocogene roxaparvovec following Patient Reported Outcome (PRO) EQ-5D-5L [ Time Frame: 52 weeks ]
    EQ-5D-5L is a general questionnaire designed to measure health status

  3. Assess the impact of valoctocogene roxaparvovec following Patient Reported Outcome (PRO) Haemophilia Activities List (HAL) [ Time Frame: 52 weeks ]
    HAL is a questionnaire that measures the impact of hemophilia on functional abilities in adults

  4. Assess the impact of valoctocogene roxaparvovec following Patient Reported Outcome (PRO) Work Productivity and Activity Impairment plus Classroom Impairment Questions: Hemophilia Specific (WPAI+CIQ:HS) [ Time Frame: 52 weeks ]
    WPAI+CIQ:HS is a questionnaire that is designed to measure the effect of symptom severity due to hemophilia on work productivity and activity/classroom impairment

  5. Assess the impact of valoctocogene roxaparvovec following Patient Reported Outcomes, Burdens, and Experiences (PROBE) Questionnaire [ Time Frame: 52 weeks ]
    PROBE is a questionnaire that is designed to investigate and directly probe patient perspectives on outcomes they deem relevant to their life and care

  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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 male genders to only be included
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.
  • Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry. High-quality, well-documented historical data concerning bleeding episodes and FVIII usage over the previous 12 months must be available.
  • Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).
  • 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) (or less than 1.0 BU for laboratories with a historical lower sensitivity cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week apart within the past 12 months (at least one of which should be tested at the central laboratory).

Exclusion Criteria:

  • Detectable pre-existing antibodies to the AAV5 capsid.
  • Any evidence of active infection or any immunosuppressive disorder, including HIV infection.
  • Significant liver dysfunction with any of the following abnormal laboratory results:

    • ALT (alanine aminotransferase) > 1.25x ULN;
    • AST (aspartate aminotransferase) > 1.25x ULN;
    • GGT (gamma-glutamyltransferase) > 1.25x ULN;
    • Total bilirubin > 1.25x ULN;
    • Alkaline phosphatase > 1.25x ULN
    • INR (international normalized ratio) ≥ 1.4.

Subjects whose liver laboratory assessments fall outside of these ranges may undergo repeat testing of the entire liver test panel within the same Screening window and, if eligibility criteria are met on retest, may be enrolled after confirmation by the Medical Monitor.

  • Prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
  • Evidence of any bleeding disorder not related to hemophilia A.
  • Platelet count of < 100 x 10^9/L.
  • Creatinine ≥ 1.5 mg/dL.
  • Liver cirrhosis of any etiology as assessed by liver ultrasound.
  • Chronic or active hepatitis B as evidenced by positive serology testing (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], and hepatitis B core antibody [HBcAb]) and confirmatory HBV DNA testing. Refer to the Centers for Disease Control (CDC) table for the interpretation of serological test results.
  • Active Hepatitis C as evidenced by detectable HCV RNA or currently on antiviral therapy.
  • Active malignancy, except non-melanoma skin cancer.
  • History of hepatic malignancy.
  • History of arterial or venous thromboembolic events (eg, deep vein thrombosis, nonhemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus), with the exception of catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing.
  • 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 identifier (NCT number): NCT03370913

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Contact: Trial Specialist 1-800-983-4587

  Hide Study Locations
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United States, California
Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center Recruiting
Los Angeles, California, United States, 90007-2664
UC Davis Hemophilia Treatment Center Recruiting
Sacramento, California, United States, 95817
University of California San Diego, Hematology and Oncology, Hemophilia &Thrombosis Treatment Center Recruiting
San Diego, California, United States, 92122
UCSF Medical Center Recruiting
San Francisco, California, United States, 94143-0106
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
St. Joseph's Children's Hospital, Center for Bleeding and Clotting Disorders Recruiting
Tampa, Florida, United States, 33607
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Hematology Recruiting
Chicago, Illinois, United States, 60611-2605
Rush University Medical Center Not yet recruiting
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Hemophilia and Thrombosis Center Recruiting
Indianapolis, Indiana, United States, 46260
United States, Kentucky
James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
United States, Louisiana
Tulane University Hematology & Medical Oncology Recruiting
New Orleans, Louisiana, United States, 70112-2699
United States, Michigan
University of Michigan, Pediatric Hematology and Oncology Recruiting
Ann Arbor, Michigan, United States, 48109-5718
Wayne State University, Detroit Medical Center Recruiting
Detroit, Michigan, United States, 48201
Michigan State University Center for Bleeding and Clotting Disorders Recruiting
East Lansing, Michigan, United States, 48823
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine, Department of Pediatrics, Division of Hematology/Oncology Recruiting
Saint Louis, Missouri, United States, 63110-1093
United States, North Carolina
UNC Hemophilia and Thrombosis Center Recruiting
Chapel Hill, North Carolina, United States, 27517
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Hemophilia Center of Western Pennsylvania Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213-4306
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37235
United States, Wisconsin
Blood Research Institute at Blood Center of Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
The Royal Adelaide Hospital (RAH) Recruiting
Adelaide, Australia
Royal Brisbane and Women's Hospital Recruiting
Brisbane, Australia
The Canberra Hospital Not yet recruiting
Canberra, Australia
Alfred Hospital Recruiting
Melbourne, Australia
Fiona Stanley Hospital Recruiting
Perth, Australia
Royal Prince Alfred Hospital Recruiting
Sydney, Australia
Saint Luc University Hospital, Hemostasis Unit Recruiting
Brussels, Belgium
University Hospital Antwerp (UZA), Department of Hematology Not yet recruiting
Edegem, Belgium
University Hospital Leuven Recruiting
Leuven, Belgium
Campinas Estadual University (UNICAMP) / Campinas Hemocentro / Hematologia E Hemoterapia Center Recruiting
Campinas, Brazil
Parana's Hematology And Hemotherapy Center (HEMEPAR) Recruiting
Curitiba, Brazil
Arthur De Siqueira Cavalcanti Hematology State Institute Recruiting
Rio De Janeiro, Brazil
Sao Paulo University Clinical Hospital Not yet recruiting
São Paulo, Brazil
Holy Spirit Hematology and Hemotherapy Center Recruiting
Vitória, Brazil
Morvan Hospital Recruiting
Brest, France
South Paris University Hospitals - Bicetre Hospital Not yet recruiting
Le Kremlin-Bicêtre, France
Regional University Hospital of Lille (CHRU de Lille) Recruiting
Lille, France
Hopital de la Timone Marseille - Assistance Publique des Hopitaux de Marseille Recruiting
Marseille, France
Hotel Dieu Hospital/Nantes University Hospital Center Not yet recruiting
Nantes, France
Cochin Hospital, Hemophilia Treament Center Not yet recruiting
Paris, France
Vivantes Clinic im Friedrichshain- Landsberger Allee Not yet recruiting
Berlin, Germany
University Clinic Bonn Not yet recruiting
Bonn, Germany
Johann Wolfgang Goethe University Hospital Not yet recruiting
Frankfurt-am-Main, Germany
Chaim Sheba Medical Center Recruiting
Ramat Gan, Israel
University Hospital Careggi, Agency of Hemophilia - Regional Reference Center for Inherited Bleeding Disorders Not yet recruiting
Florence, Italy
Maggiore Polyclinic Hospital, IRCCS Ca' Granda, Center for Hemophilia and Thrombosis Angelo Bianchi Bonomi Recruiting
Milan, Italy
Korea, Republic of
Pusan National University Hospital Not yet recruiting
Busan, Korea, Republic of
Kyungpook National University Hospital Not yet recruiting
Daegu, Korea, Republic of
Department of Pediatrics, Kyung Hee University Hospital at Gangdong Recruiting
Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System Not yet recruiting
Seoul, Korea, Republic of
Ulsan University Hospital Not yet recruiting
Ulsan, Korea, Republic of
South Africa
Groote Schuur Hospital Not yet recruiting
Cape Town, South Africa
Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center Recruiting
Johannesburg, South Africa
Hospital Teresa Herrera Recruiting
A Coruna, Spain
University Hospital Vall d'Hebron (HUVH) Not yet recruiting
Barcelona, Spain
University Hospital La Paz Not yet recruiting
Madrid, Spain
Hospital Regional Universitario de Málaga Not yet recruiting
Málaga, Spain
University Hospital Virgen del Rocio (HUVR) Recruiting
Seville, Spain
Changhua Christian Hospital Recruiting
Changhua, 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
Tri-Service General Hospital Recruiting
Taipei, Taiwan
United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom
Addenbrookes Hospital Recruiting
Cambridge, United Kingdom
Glasgow Royal Infirmary, Department of Hematology Recruiting
Glasgow, United Kingdom
Barts and The London School of Medicine and Dentistry, Haemophilia Centre Recruiting
London, United Kingdom
Hammersmith Recruiting
London, United Kingdom
St Thomas' Hospital Recruiting
London, United Kingdom
Churchill Hospital, Oxford Hemophilia and Thrombosis Center Recruiting
Oxford, United Kingdom
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, United Kingdom
Royal Cornwall Hospital, Department of Hematology Recruiting
Truro, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: Medical Monitor, MD BioMarin Pharmaceutical

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Responsible Party: BioMarin Pharmaceutical Identifier: NCT03370913     History of Changes
Other Study ID Numbers: BMN 270-301
2017-003215-19 ( EudraCT Number )
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: November 11, 2019
Last Verified: November 2019

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