Phase 3 Study for Efficacy and Safety Outcomes Data in Japanese Patients With Severe Hemophilia A

NCT06224907 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: 270-304
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

This Phase III clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in Japanese patients with severe hemophilia A.

Conditions

Hemophilia A

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in the human coagulation factor VIII (hFVIII) activity, as measured by chromogenic substrate assay, during Weeks 49 to 52 post BMN 270 infusion from Baseline.

  The change from baseline in FVIII activity, as measured by chromogenic substrate assay, during Weeks 49 to 52 post-BMN 270 infusion. Each subject's FVIII activity level during Week 49 to 52 is defined as the median of the values obtained during week 49-52 with the analysis window defined. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. The baseline value is imputed as 1 IU/dL for each subject.

  52 Weeks

Secondary Outcomes (4)

• Change in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the efficacy evaluation period (EEP) ("Post FVIII Prophylaxis to Last Visit") from the Baseline utilization of exogenous FVIII replacement therapy.

  Baseline to at least Week 52

• Change in the annualized bleeding rate (i.e., number of bleeding episodes per year) requiring exogenous FVIII replacement treatment therapy in the efficacy evaluation period ("Post FVIII Prophylaxis to Last Visit") from Baseline.

  Baseline to at least Week 52

• Change from Baseline in Hemophilia-Specific Health-Related Quality of Life Questionnaire for Adults (Haemo-QoL-A) total score, physical functioning, role functioning, and consequences of bleeding domain scores at Week 52 of study post-BMN 270 infusion

  Baseline to Week 52

• Change from Baseline in the Haemo-QoL-A worry, emotional impact, and treatment concern domain scores at Week 52 of the study post-BMN 270 infusion.

  Baseline to Week 52

Study Arms (1)

Valoctocogene roxaparvovec

EXPERIMENTAL

Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg

Biological: Valoctocogene roxaparvovec

Interventions

Valoctocogene roxaparvovec BIOLOGICAL

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

Also known as: BMN 270, ROCTAVIAN

Valoctocogene roxaparvovec

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Japanese males ≥18 years of age with HA and endogenous FVIII activity levels \<1 IU/dL as evidenced by medical history, at the time of signing the informed consent
• Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry. High-quality, well-documented historical data concerning bleeding episodes and FVIII usage over the previous 12 months must be available.
• Treated/exposed to FVIII concentrates for a minimum of 150 exposure days.
• Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study-related procedures.
• 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) or less than 1.0 BU for laboratories with a historical lower sensitivity cutoff for inhibitor detection of 1.0 BU on 2 consecutive occasions at least 1 week apart within the past 12 months (at least 1 of which should be tested at the central laboratory).
• Sexually active participants must agree to use an acceptable method of effective contraception
• Willing to abstain from alcohol consumption 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, except for human immunodeficiency virus (HIV) infection. HIV-positive participants who meet all other eligibility criteria may be included.
• Significant liver dysfunction
• Most recent, prior FibroScan or liver biopsy showing significant fibrosis
• Evidence of any bleeding disorder not related to HA.
• Platelet count of \<100E9/L.
• Creatinine ≥1.5 mg/dL.
• Liver cirrhosis of any etiology as assessed by liver ultrasound.
• Chronic or active hepatitis B
• Active hepatitis C
• Active malignancy, except non-melanoma skin cancer
• History of hepatic malignancy
• History of arterial or venous thromboembolic events
• Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation
• Treatment with any investigational product (IP) within 30 days or 5 half-lives of the IP prior to the Screening period.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (4)

Asahikawa Medical University Hospital

Hokkaido, Asahikawa, 078-8510, Japan

Location

Saitama Medical University Hospital

Saitama, Iruma-gun, 350-0495, Japan

Location

Nagoya University Hospital

Aichi, Nagoya, 466-8560, Japan

Location

Tokyo Medical University Hospital

Tokyo, Shinjuku-ku, 160-0023, Japan

Location

MeSH Terms

Conditions

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

Interventions

Valoctocogene Roxaparvovec

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Monitor, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 25, 2024
• Study Start: December 25, 2023
• Primary Completion: April 16, 2025
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

JP (4)