Safety, Tolerability, and Efficacy Study of Valoctocogene Roxaparvovec in Hemophilia A With Active or Prior Inhibitors

Phase 1

Active, not recruiting

• Conditions: Hemophilia A With Anti Factor VIII; Hemophilia A With Inhibitor
• Interventions: Biological: Valoctocogene roxaparvovec

• Registration Number: NCT04684940
• Lead Sponsor: BioMarin Pharmaceutical

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 available

Study Timeline

• Study First Submitted: 2020-11-30
• Study Start: 2020-12-10
• Study First Submitted QC: 2020-12-24
• Study First Posted: 2020-12-28
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-03
• Last Update Posted: 2024-07-05
• Primary Completion: 2029-04
• Study Completion: 2029-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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.	60 months

Secondary Outcome Measures

Name	Time	Method
Change of the median Factor VIII activity.	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.	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.	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	60 months
Change in the annualized number of bleeding episodes requiring exogenous hemophilia therapy after administration of BMN 270.	60 months

Trial Locations

Locations (9)

Kaohsiung Medical University - Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Chaim Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Kyung Hee University Hospital at Gangdong; 🇰🇷 Seoul, Korea, Republic of

Arthur De Siqueira Cavalcanti Hematology State Institute; 🇧🇷 Rio De Janeiro, Brazil

Hemocentro Da UNICAMP; 🇧🇷 Campinas, Brazil

Ege University School of Medicine; 🇹🇷 Izmir, Turkey

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan