Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)

NCT ID: NCT03370913

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-19
• Study Completion Date: 2024-11-20

Brief Summary

This Phase III clinical study will assess the impact of BMN 270 (compared to FVIII prophylaxis) on the number of bleeding episodes irrespective of exogenous FVIII replacement treatment in the efficacy evaluation period (EEP) (from Week 5 post-BMN 270 infusion (Study Day 33) or the end of FVIII prophylaxis plus the washout period (3 days for products of standard half-life or plasma-derived and 5 days for products of extended half-life), whichever is later, to last visit by the data cut-off for the 2-year analysis, hereafter referred to as "Post FVIII Prophylaxis to Last Visit"). The study will also assess the impact of BMN 270 (compared to FVIII prophylaxis) on: the number of bleeding episodes requiring exogenous FVIII treatment in "Post FVIII Prophylaxis to Last Visit", FVIII activity as measured by chromogenic sustrate assay at Week 104 following intravenous infusion of BMN 270, usage of exogenous FVIII replacement therapy in "Post FVIII Prophylaxis to Last Visit", health-related quality of life patient-reported outcomes at week 104 following intravenous infusion of BMN 270. The study will also evaluate the safety of the BMN 270.

Conditions

Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

valoctocogene roxaparvovec Open Label

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

Group Type: EXPERIMENTAL

valoctocogene roxaparvovec

Intervention Type: BIOLOGICAL

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

Interventions

valoctocogene roxaparvovec

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

Intervention Type: BIOLOGICAL

Other Intervention Names

BMN 270

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry.

3. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs).

4. 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) on 2 consecutive occasions at least one week apart within the past 12 months.

Exclusion Criteria

1. Detectable pre-existing antibodies to the adeno-associated virus 5 (AAV5) capsid.

2. Any evidence of active infection or any immunosuppressive disorder, except for HIV infection

3. Any evidence of active infection or any immunosuppressive disorder, including HIV infection (effective as of Protocol Amendment 3)

4. Significant liver dysfunction.

5. Prior liver biopsy showing significant fibrosis.

6. Evidence of any bleeding disorder not related to hemophilia A.

7. Platelet count of < 100 x 10^9/L.

8. Creatinine ≥ 1.5 mg/dL.

9. Liver cirrhosis of any etiology as assessed by liver ultrasound.

10. Chronic or active hepatitis B.

11. Active Hepatitis C.

12. Active malignancy, except non-melanoma skin cancer.

13. History of hepatic malignancy.

14. History of arterial or venous thromboembolic events.

15. Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center

Los Angeles, California, United States

UC Davis Hemophilia Treatment Center

Sacramento, California, United States

University of California San Diego, Hematology and Oncology, Hemophilia &Thrombosis Treatment Center

San Diego, California, United States

UCSF Medical Center

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

St. Joseph's Children's Hospital, Center for Bleeding and Clotting Disorders

Tampa, Florida, United States

Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Hematology

Chicago, Illinois, United States

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Tulane University Hematology & Medical Oncology

New Orleans, Louisiana, United States

University of Michigan, Pediatric Hematology and Oncology

Ann Arbor, Michigan, United States

Wayne State University, Detroit Medical Center

Detroit, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University School of Medicine, Department of Pediatrics, Division of Hematology/Oncology

St Louis, Missouri, United States

UNC Hemophilia and Thrombosis Center

Chapel Hill, North Carolina, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

The Royal Adelaide Hospital (RAH)

Adelaide, , Australia

Royal Brisbane and Women's Hospital

Brisbane, , Australia

Alfred Hospital

Melbourne, , Australia

Fiona Stanley Hospital

Perth, , Australia

Royal Prince Alfred Hospital

Sydney, , Australia

University Hospital Leuven

Leuven, , Belgium

Campinas Estadual University (UNICAMP) / Campinas Hemocentro / Hematologia E Hemoterapia Center

Campinas, , Brazil

Parana's Hematology And Hemotherapy Center (HEMEPAR)

Curitiba, , Brazil

Arthur De Siqueira Cavalcanti Hematology State Institute

Rio de Janeiro, , Brazil

Sao Paulo University Clinical Hospital

São Paulo, , Brazil

Holy Spirit Hematology and Hemotherapy Center

Vitória, , Brazil

Regional University Hospital of Lille (CHRU de Lille)

Lille, , France

Hopital de la Timone Marseille - Assistance Publique des Hopitaux de Marseille

Marseille, , France

Vivantes Clinic im Friedrichshain- Landsberger Allee

Berlin, , Germany

University Clinic Bonn

Bonn, , Germany

Chaim Sheba Medical Center

Ramat Gan, , Israel

Maggiore Polyclinic Hospital, IRCCS Ca' Granda, Center for Hemophilia and Thrombosis Angelo Bianchi Bonomi

Milan, , Italy

Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center

Johannesburg, , South Africa

Department of Pediatrics, Kyung Hee University Hospital at Gangdong

Seoul, , South Korea

Hospital Teresa Herrera

A Coruña, , Spain

University Hospital Virgen del Rocio (HUVR)

Seville, , Spain

Changhua Christian Hospital

Changhua, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Addenbrookes Hospital

Cambridge, , United Kingdom

Glasgow Royal Infirmary, Department of Hematology

Glasgow, , United Kingdom

Barts and The London School of Medicine and Dentistry, Haemophilia Centre

London, , United Kingdom

Hammersmith

London, , United Kingdom

St Thomas' Hospital

London, , United Kingdom

Churchill Hospital, Oxford Hemophilia and Thrombosis Center

Oxford, , United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; France; Germany; Israel; Italy; South Africa; South Korea; Spain; Taiwan; United Kingdom

References

Santos S, Robinson TM, Trueman D. Estimated Long-Term Durability of Valoctocogene Roxaparvovec Treatment in Male patients with Severe Hemophilia A: An Extrapolation of Clinical Data. Adv Ther. 2025 Sep 23. doi: 10.1007/s12325-025-03368-4. Online ahead of print.

Reference Type: DERIVED

PMID: 40986187 (View on PubMed)

Agarwal S, Sandza K, Obrochta Moss K, Vora M, Bowen A, Bunch B, Holcomb J, Robinson TM, Jayaram K, Russell CB, Zoog S, Vettermann C, Henshaw J. Blood biodistribution and vector shedding of valoctocogene roxaparvovec in people with severe hemophilia A. Blood Adv. 2024 Sep 10;8(17):4606-4615. doi: 10.1182/bloodadvances.2024013150.

Reference Type: DERIVED

PMID: 39024543 (View on PubMed)

Oldenburg J, Chambost H, Liu H, Hawes C, You X, Yang X, Newman V, Robinson TM, Hatswell AJ, Hinds D, Santos S, Ozelo M. Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A. Adv Ther. 2024 Jun;41(6):2267-2281. doi: 10.1007/s12325-024-02834-9. Epub 2024 Apr 15.

Reference Type: DERIVED

PMID: 38616241 (View on PubMed)

Mahlangu J, Kaczmarek R, von Drygalski A, Shapiro S, Chou SC, Ozelo MC, Kenet G, Peyvandi F, Wang M, Madan B, Key NS, Laffan M, Dunn AL, Mason J, Quon DV, Symington E, Leavitt AD, Oldenburg J, Chambost H, Reding MT, Jayaram K, Yu H, Mahajan R, Chavele KM, Reddy DB, Henshaw J, Robinson TM, Wong WY, Pipe SW; GENEr8-1 Trial Group. Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A. N Engl J Med. 2023 Feb 23;388(8):694-705. doi: 10.1056/NEJMoa2211075.

Reference Type: DERIVED

PMID: 36812433 (View on PubMed)

Quinn J, Delaney KA, Wong WY, Miesbach W, Bullinger M. Psychometric Validation of the Haemo-QOL-A in Participants with Hemophilia A Treated with Gene Therapy. Patient Relat Outcome Meas. 2022 Jul 18;13:169-180. doi: 10.2147/PROM.S357555. eCollection 2022.

Reference Type: DERIVED

PMID: 35879931 (View on PubMed)

Ozelo MC, Mahlangu J, Pasi KJ, Giermasz A, Leavitt AD, Laffan M, Symington E, Quon DV, Wang JD, Peerlinck K, Pipe SW, Madan B, Key NS, Pierce GF, O'Mahony B, Kaczmarek R, Henshaw J, Lawal A, Jayaram K, Huang M, Yang X, Wong WY, Kim B; GENEr8-1 Trial Group. Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. N Engl J Med. 2022 Mar 17;386(11):1013-1025. doi: 10.1056/NEJMoa2113708.

Reference Type: DERIVED

PMID: 35294811 (View on PubMed)

Rosen S, Tiefenbacher S, Robinson M, Huang M, Srimani J, Mackenzie D, Christianson T, Pasi KJ, Rangarajan S, Symington E, Giermasz A, Pierce GF, Kim B, Zoog SJ, Vettermann C. Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy. Blood. 2020 Nov 26;136(22):2524-2534. doi: 10.1182/blood.2020005683.

Reference Type: DERIVED

PMID: 32915950 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-003215-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

270-301

Identifier Type: -

Identifier Source: org_study_id