Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients at a Dose of 4E13 vg/kg (GENEr8-2)

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 at a Dose of 4E13vg/kg in Hemophilia A Patients With Residual FVIII Levels ≤1IU/dL Receiving Prophylactic FVIII Infusions

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: Valoctocogene Roxaparvovec

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-4306
      • Hemophilia Center of Western Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males ≥ 18 years of age with hemophilia A and residual FVIII levels ≤ 1 IU/dL as evidenced by medical history.
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.
4. No previous documented history of a detectable FVIII inhibitor of less than 0.6 Bethesda Units (BU).

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, prior liver biopsy showing significant fibrosis, liver cirrhosis of any etiology or history of hepatic malignancy.
4. Evidence of any bleeding disorder not related to hemophilia A.
5. Active Hepatitis C.
6. Prior treatment with any vector/gene transfer agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: BMN 270

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the Median Factor VIII (FVIII) Activity	Change of the FVIII activity, as measured by chromogenic substrate assay, at Week 52 post-BMN 270 infusion.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Annualized Utilization (IU/kg) of Exogenous FVIII Replacement Therapy	Change in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy during Week 5 to Week 52 post-BMN 270 infusion from the baseline utilization of exogenous FVIII replacement therapy	Weeks 5 through Week 52
Change in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment	Change in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment (annualized bleeding rate, ABR) during Week 5 to Week 52 of the study post-BMN 270 infusion from the baseline ABR	Weeks 5 though Week 52

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Director, MD, BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2018
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): June 5, 2023

Study Registration Dates

• First Submitted: December 22, 2017
• First Submitted That Met QC Criteria: January 4, 2018
• First Posted (Actual): January 8, 2018

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Gene Therapy; Hematologic Diseases; Blood Coagulation Disorders; Factor VIII; Genetic Diseases; Hemorrhagic Disorders; Hemophilia A; Coagulants; Inborn; Clotting Disorders; Blood Disorder; Inherited Blood Coagulation Disorders; Coagulation Protein Disorders
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: 270-302; 2017-003573-34 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No