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Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg (BMN270-302)

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. Identifier: NCT03392974
Recruitment Status : Active, not recruiting
First Posted : January 8, 2018
Last Update Posted : September 6, 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 4E13 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 : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3 Study To Evaluate Efficacy/Safety of Valoctocogene Roxaparvovec an AAV Vector-Mediated Gene Transfer of hFVIII at a Dose of 4E13vg/kg in Hemophilia A Patients With Residual FVIII Levels ≤1IU/dL Receiving Prophylactic FVIII Infusions
Actual Study Start Date : March 14, 2018
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : March 1, 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Valoctocogene Roxaparvovec Open Label
Single administration of valoctocogene roxaparvovec at a dose of 4E13 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 Factor VIII (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 on a scale of 0-5 with the lower value representing a better outcome

  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 on a scale of 0-100 with the higher value representing a better outcome

  3. Assess the impact of valoctocogene roxaparvovec following Patient Reported Outcome (PRO) Haemophilia Activities List (HAL) [ Time Frame: 5 years ]
    HAL is a questionnaire that has several activities are listed that could be difficult for people with hemophilia. The aim of the questionnaire is to see how easy it is for participates to do those activities.

  4. 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

  5. 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

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; or
    • 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 and confirmatory HBV DNA testing. Refer to the Centers for Disease Control (CDC) table for the interpretation of serological test results in the Laboratory Manual.
  • 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.

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): NCT03392974

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Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: Medical Director, MD BioMarin Pharmaceutical
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Responsible Party: BioMarin Pharmaceutical Identifier: NCT03392974    
Other Study ID Numbers: BMN 270-302
2017-003573-34 ( EudraCT Number )
First Posted: January 8, 2018    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 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:
Hemophilia A
Gene Therapy
Clotting Disorders
Blood Disorder
Blood Coagulation Disorders
Inherited Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases
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