Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors (GENEr8-INH)

• ClinicalTrials.gov Identifier: NCT04684940
• Recruitment Status: Recruiting
• First Posted: December 28, 2020
• Last Update Posted: April 24, 2024
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

Tracking Information

• First Submitted Date: November 30, 2020
• First Posted Date: December 28, 2020
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: December 10, 2020
• Estimated Primary Completion Date: February 2029 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 24, 2020): Number of participants with treatment-related adverse events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 after administration of BMN 270. [ Time Frame: 60 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2022)

• Change of the median Factor VIII activity. [ Time Frame: 60 months ]
  Changes in the median Factor VIII activity (IU/mL) after administration of BMN 270 which will be measured using the chromogenic FVIII assay.
• A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270. [ Time Frame: 60 months ]
  FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
• Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270. [ Time Frame: 60 months ]
  FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
• Change in the annualized utilization of hemophilia therapy after administration of BMN 270 [ Time Frame: 60 months ]
• Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270. [ Time Frame: 60 months ]

Original Secondary Outcome Measures (submitted: December 24, 2020)

• Change of the median Factor VIII activity. [ Time Frame: 60 months ]
  Changes in the median Factor VIII activity (IU/mL) after administration of BMN 270 which will be measured using the chromogenic FVIII assay.
• A decrease in Factor VIII inhibitor titer (Part A) after administration of BMN 270. [ Time Frame: 60 months ]
  FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
• Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270. [ Time Frame: 60 months ]
  FVIII inhibitor titer will be measured using a chromogenic Nijmegen-Bethesda assay.
• Change in the annualized utilization (IU/kg) of emicizumab and exogenous FVIII replacement therapy for subjects receiving emicizumab or FVIII prophylaxis respectively after administration of BMN 270. [ Time Frame: 60 months ]
• Change in the annualized number of bleeding episodes requiring exogenous emicizumab or FVIII replacement treatment after administration of BMN 270. [ Time Frame: 60 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors
• Official Title: A Phase 1/2 Safety, Tolerability, and Efficacy Study of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Active or Prior Inhibitors
• Brief Summary: This Phase I/II clinical study will evaluate the safety and efficacy of valoctocogene roxaparvovec in patients with severe haemophilia A and inhibitors to FVIII. Part A of the study will involve subjects who have active inhibitors to FVIII, and Part B involving subjects with a prior history of inhibitors.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hemophilia A With Inhibitor
• Hemophilia A With Anti Factor VIII

Intervention

Biological: Valoctocogene roxaparvovec

Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A

Other Name: BMN 270 (GENEr8)

Study Arms

Experimental: Valoctocogene roxaparvovec Open Label

Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg in Active Inhibitor Population (Part A) and Prior Inhibitor Population (Part B).

Intervention: Biological: Valoctocogene roxaparvovec

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 24, 2020): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2029
• Estimated Primary Completion Date: February 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Males ≥ 18 years of age with hemophilia A and documented prior residual FVIII activity ≤ 1 IU/dL including, but not limited to, at the time of detected inhibitors, at the time of signing the informed consent.

2. History of a positive inhibitor result with the first positive result at least 12 month prior to Screening.

   Part A: Demonstrated no immunological tolerance to exogenous FVIII. Part B: Demonstrated tolerance to exogenous FVIII and negative FVIII inhibitor screening titer < 0.6 BU.

3. Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor & hemophilia therapy Hx over previous 12 months.
4. Sexually active participants must agree to use an acceptable method of effective contraception. Participants must agree to contraception use for at least 12 weeks post-infusion.
5. Willing to abstain from consumption of alcohol for at least the first 52 weeks following BMN 270 infusion.

Exclusion Criteria:

1. Detectable pre-existing antibodies to the AAV5 capsid.
2. Any evidence of active infection or any immunosuppressive disorder; patients with HIV infection and undetectable viral load are not excluded.
3. Currently undergoing, or plan to receive during the study, immune tolerance induction therapy or prophylaxis with FVIII (Part A only).
4. Significant renal dysfunction or liver dysfunction, infection or history of hepatic malignancy.
5. Evidence of any bleeding disorder not related to hemophilia A.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Biological males only

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Specialist; 1-800-983-4587; medinfo@bmrn.com

• Listed Location Countries: Brazil, Germany, Israel, Italy, Korea, Republic of, South Africa, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04684940
• Other Study ID Numbers: 270-205; 2019-003213-34 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioMarin Pharmaceutical
• Original Responsible Party: Same as current
• Current Study Sponsor: BioMarin Pharmaceutical
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor, MD; BioMarin Pharmaceutical

• PRS Account: BioMarin Pharmaceutical
• Verification Date: April 2024