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

NCT04684940 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 270-2052019-003213-34
• Study Type: interventional
• Target: 10
• Locations: 6 countries
• Sites: 9

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.

Conditions

Hemophilia A With Inhibitor; Hemophilia A With Anti Factor VIII

Keywords

Gene Therapy; Clotting Disorders; Blood Disorder; Blood Coagulation Disorders; Inherited Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic DIseases; Factor VIII; Coagulants; Hemophilia A; AAV5 vector

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change of the median Factor VIII activity.

  60 months

• A change in Factor VIII inhibitor titer (Part A) after administration of BMN 270.

  60 months

• Absence of recurrence of Factor VIII inhibitors (Part B) after administration of BMN 270.

  60 months

• 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

Study Arms (1)

Valoctocogene roxaparvovec Open Label

EXPERIMENTAL

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

Biological: Valoctocogene roxaparvovec

Interventions

Valoctocogene roxaparvovec BIOLOGICAL

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

Also known as: BMN 270 (GENEr8)

Valoctocogene roxaparvovec Open Label

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Biological males only
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Prophylactic or on-demand hemophilia therapy in the last 12 months. Bleeding, inhibitor \& hemophilia therapy Hx over previous 12 months.
• 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.
• Willing to abstain from consumption of alcohol for at least the first 52 weeks following BMN 270 infusion.

You may not qualify if:

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

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (9)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Hemocentro Da UNICAMP

Campinas, Brazil

Location

Arthur De Siqueira Cavalcanti Hematology State Institute

Rio de Janeiro, Brazil

Location

Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Kyung Hee University Hospital at Gangdong

Seoul, South Korea

Location

Kaohsiung Medical University - Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Ege University School of Medicine

Izmir, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Hemostatic Disorders; Hematologic Diseases; Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Hemophilia A

Interventions

Valoctocogene Roxaparvovec

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Medical Monitor, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 28, 2020
• Study Start: December 10, 2020
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1); IL (1); TW (3); TU (1); BR (2); US (1)