Study to Evaluate the Efficacy and Safety of Valoctocogene Roxaparvovec, With Prophylactic Steroids in Hemophilia A

NCT04323098 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 270-303
• Study Type: interventional
• Target: 22
• Locations: 4 countries
• Sites: 12

Brief Summary

This Phase III clinical study will evaluate the safety and effectiveness of valoctocogene roxaparvovec in combination with prophylactic corticosteroids in 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; Factor VIII; Coagulants

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in FVIII Activity as Measured by Chromogenic Substrate Assay at Week 52.

  The change from baseline (assuming no treatment for severe hemophilia A) in FVIII activity, as measured by chromogenic substrate assay (CSA), at Week 52 (during Weeks 49 - 52) post-BMN 270 infusion. Each participant's FVIII activity level at Week 52 is defined as the median of the values obtained within the analysis window at Weeks 49-52. The baseline value will be imputed as 1 IU/dL, since there will be no washout of severe hemophilia A participants' usual FVIII prophylaxis (in order to avoid increasing the risk of bleeding) prior to BMN 270 infusion. Post-BMN 270 infusion values for FVIII activity will be excluded from analysis if obtained within 72 hours (or 3 calendar days if time is not available) since the last infusion of exogenous FVIII replacement therapy. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis.

  Baseline to Week 52

Secondary Outcomes (7)

• Change From Baseline in Annualized Utilization of Exogenous FVIII Replacement Therapy in EEP

  Baseline to efficacy evaluation period (EEP)

• Change From Baseline in the Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment (Annualized Bleeding Rate, ABR for All Bleeds) in EEP

  Baseline to efficacy evaluation period (EEP)

• Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Treatment (ABR for Treated Bleeds) in the EEP.

  Baseline to EEP

• Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 52

  Baseline to Week 52

• Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 52

  Baseline to Week 52

Study Arms (1)

valoctocogene roxaparvovec

EXPERIMENTAL

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

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

valoctocogene roxaparvovec

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 residual FVIII levels \<= 1 IU/dL as evidenced by medical history, at the time of signing the informed consent.
• Must have been on prophylactic hemophilia therapy for at least 12 months prior to study entry. High-quality, well-documented historical data concerning bleeding episodes and hemophilia therapy usage over the previous 12 months must be available.
• Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).
• 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 one week apart within the past 12 months (at least one of which should be tested at the central laboratory).
• Sexually active participants must agree to use an acceptable method of effective contraception, either double-barrier contraception (ie, condom + diaphragm; or condom or diaphragm + spermicidal gel or foam) or their female partner either using hormonal contraceptives or having an intrauterine device. Participants must agree to contraception use for at least 12 weeks post-infusion; after 12 weeks, participants may stop contraception use only if they have had 3 consecutive semen samples with viral vector DNA below the limit of detection.
• Willing to abstain from alcohol consumption for at least the first 52 weeks following BMN 270 infusion.

You may not qualify if:

• Participants with detectable pre-existing antibodies to the adeno-associated virus (AAV5) capsid are excluded with the following exception: up to 25% of participants may have detectable pre-existing AAV5 capsid antibodies with titer level below the minimum required dilution (\< 20).
• Any evidence of active infection, including Coronavirus Disease (COVID-19), or any immunosuppressive disorder, except for HIV infection. HIV-positive patients who meet all other eligibility criteria may be included if they have a CD4 count \> 200/mm\^3 and an undetectable viral load (unquantifiable viral load as defined as less than the limit of quantification by the testing laboratory's assay is permitted) while receiving an antiretroviral therapy (ART) regimen that does not contain efavirenz or another potentially hepatotoxic ART.
• Significant liver dysfunction with any of the following abnormal laboratory results: alanine aminotransferase (ALT) \> 1.25x upper limit of normal (ULN);aspartate aminotransferase (AST) \> 1.25x ULN;gamma-glutamyltransferase (GGT) \> 1.25x ULN;Total bilirubin \> 1.25x ULN;Alkaline phosphatase \> 1.25x ULN; or international normalized ratio (INR) \>= 1.4.
• Participants whose liver laboratory assessments fall outside of these ranges could undergo repeat testing of the entire liver test panel within the same Screening window and, if eligibility criteria are met on retest, could be enrolled after confirmation by the Medical Monitor.
• FibroScan or prior liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
• Evidence of any bleeding disorder not related to hemophilia A.
• Platelet count of \< 100 x 10\^9/L.
• Creatinine \>= 1.5 mg/dL
• Liver cirrhosis or other clinically significant liver disease of any etiology as assessed by FibroScan or liver ultrasound.
• Chronic or active hepatitis B as evidenced by positive serology testing (hepatitis B surface antigen \[HBsAg\], hepatitis B surface antibody \[HBsAb\], and hepatitis B core antibody \[HBcAb\]) and confirmatory hepatitis B virus (HBV) DNA testing. Refer to the Centers for Disease Control (CDC) table for the interpretation of serological test results in the Laboratory Manual.
• Active Hepatitis C as evidenced by detectable hepatitis C virus (HCV) RNA or currently on antiviral therapy.
• Active malignancy, except non-melanoma skin cancer.
• History of hepatic malignancy.
• History of arterial or venous thromboembolic events (eg, deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus), with the exception of catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing.
• Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (12)

University of California Davis Health

Sacramento, California, 95817, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Royal Adelaide Hospital

Adelaide, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Australia

Location

Alfred Hospital

Melbourne, Australia

Location

Fiona Stanley Hospital

Perth, Australia

Location

Royal Prince Alfred Hospital

Sydney, Australia

Location

Campinas University Clinical Hospital

Campinas, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, Brazil

Location

Changhua Christian Medical Foundation Changhua Christian Hospital

Changhua, Taiwan

Location

Taichung Veterans General Hospital

Taichung, Taiwan

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

Results Point of Contact

• Title: Tara M Robinson, MD, PhD, Senior Medical Director, Late-Stage Clinical Development
• Organization: BioMarin Pharmaceutical Inc.

tara.robinson@bmrn.com

415-455-7931

Study Officials

• Medical Monitor, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: March 24, 2020
• First Posted: March 26, 2020
• Study Start: December 8, 2020
• Primary Completion: January 27, 2023
• Study Completion: May 8, 2025
• Last Updated: October 8, 2025
• Results First Posted: April 4, 2024

Record last verified: 2025-09

Locations

BR (2); US (3); AU (5); TW (2)