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Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301) (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 : December 23, 2022
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Study Description
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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
Hemophilia A Biological: valoctocogene roxaparvovec Phase 3

Study Design
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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
Actual Primary Completion Date : November 16, 2020
Estimated Study Completion Date : November 2024

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


Outcome Measures
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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 [ Time Frame: 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 [ Time Frame: 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 [ 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 ]

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 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
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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): NCT03370913


Locations
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Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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Study Director: Medical Monitor, MD BioMarin Pharmaceutical
More Information
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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: December 23, 2022
Last Verified: December 2022

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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
Inborn
Factor VIII
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