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

NCT03370913 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 270-3012017-003215-19
• Study Type: interventional
• Target: 144
• Locations: 13 countries
• Sites: 49

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

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 From Baseline in Annualized Number of Bleeding Episodes Irrespective of Exogenous FVIII Replacement Treatment [Annualized Bleeding Rate (ABR) for All Bleeds] in EEP.

  All bleeds comprises both treated and non-treated bleeds. In this definition, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. All bleeds are any reported bleeding events regardless of the use of FVIII or other treatments. ABR for all bleeds= Number of bleeding episodes for all bleeds during the calculation period / total number of days during the calculation period \* 365.25. Baseline: prior to BMN 270 infusion while receiving FVIII prophylaxis. 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").

  Baseline to efficacy evaluation period (EEP)

Secondary Outcomes (7)

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

  Baseline to EEP

• Change From Baseline in FVIII Activity at Week 104

  Baseline to Week 104

• Change From Baseline in Annualized FVIII Utilization in EEP.

  Baseline to EEP

• Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 104

  Baseline to Week 104

• Change From Baseline in Haemo-QoL-A Quality of Life: Physical Functioning Domain Score, at Week 104

  Baseline to Week 104

Study Arms (1)

valoctocogene roxaparvovec Open Label

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 Hemophilia A

Also known as: BMN 270

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

You may not qualify if:

• Detectable pre-existing antibodies to the adeno-associated virus 5 (AAV5) capsid.
• Any evidence of active infection or any immunosuppressive disorder, except for HIV infection
• Any evidence of active infection or any immunosuppressive disorder, including HIV infection (effective as of Protocol Amendment 3)
• Significant liver dysfunction.
• Prior liver biopsy showing significant fibrosis.
• 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 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (49)

Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center

Los Angeles, California, 90007-2664, United States

Location

UC Davis Hemophilia Treatment Center

Sacramento, California, 95817, United States

Location

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

San Diego, California, 92122, United States

Location

UCSF Medical Center

San Francisco, California, 94143-0106, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

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

Tampa, Florida, 33607, United States

Location

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

Chicago, Illinois, 60611-2605, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Tulane University Hematology & Medical Oncology

New Orleans, Louisiana, 70112-2699, United States

Location

University of Michigan, Pediatric Hematology and Oncology

Ann Arbor, Michigan, 48109-5718, United States

Location

Wayne State University, Detroit Medical Center

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

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

St Louis, Missouri, 63110-1093, United States

Location

UNC Hemophilia and Thrombosis Center

Chapel Hill, North Carolina, 27517, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Royal Adelaide Hospital (RAH)

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

University Hospital Leuven

Leuven, Belgium

Location

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

Campinas, Brazil

Location

Parana's Hematology And Hemotherapy Center (HEMEPAR)

Curitiba, Brazil

Location

Arthur De Siqueira Cavalcanti Hematology State Institute

Rio de Janeiro, Brazil

Location

Sao Paulo University Clinical Hospital

São Paulo, Brazil

Location

Holy Spirit Hematology and Hemotherapy Center

Vitória, Brazil

Location

Regional University Hospital of Lille (CHRU de Lille)

Lille, France

Location

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

Marseille, France

Location

Vivantes Clinic im Friedrichshain- Landsberger Allee

Berlin, Germany

Location

University Clinic Bonn

Bonn, Germany

Location

Chaim Sheba Medical Center

Ramat Gan, Israel

Location

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

Milan, Italy

Location

Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center

Johannesburg, South Africa

Location

Department of Pediatrics, Kyung Hee University Hospital at Gangdong

Seoul, South Korea

Location

Hospital Teresa Herrera

A Coruña, Spain

Location

University Hospital Virgen del Rocio (HUVR)

Seville, Spain

Location

Changhua Christian Hospital

Changhua, Taiwan

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

Tri-Service General Hospital

Taipei, Taiwan

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Addenbrookes Hospital

Cambridge, United Kingdom

Location

Glasgow Royal Infirmary, Department of Hematology

Glasgow, United Kingdom

Location

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

London, United Kingdom

Location

Hammersmith

London, United Kingdom

Location

St Thomas' Hospital

London, United Kingdom

Location

Churchill Hospital, Oxford Hemophilia and Thrombosis Center

Oxford, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

Related Publications (7)

• 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 Nov;42(11):5781-5793. doi: 10.1007/s12325-025-03368-4. Epub 2025 Sep 23.

  PMID: 40986187 DERIVED

• 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.

  PMID: 39024543 DERIVED

• 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.

  PMID: 38616241 DERIVED

• 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.

  PMID: 36812433 DERIVED

• 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.

  PMID: 35879931 DERIVED

• 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.

  PMID: 35294811 DERIVED

• 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.

  PMID: 32915950 DERIVED

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 Robinson, MD, PhD, Senior Medical Director, Clinical Sciences
• 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: November 27, 2017
• First Posted: December 13, 2017
• Study Start: December 19, 2017
• Primary Completion: November 16, 2020
• Study Completion: November 20, 2024
• Last Updated: March 25, 2025
• Results First Posted: November 28, 2023

Record last verified: 2025-03

Locations

TW (5); DE (2); IL (1); BE (1); KR (1); ZA (1); IT (1); AU (5); BR (5); FR (2); ES (2); GB (8); US (15)