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

Primary Purpose

Hemophilia A

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
valoctocogene roxaparvovec
Sponsored by
BioMarin Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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 AAV5 capsid.
  2. Any evidence of active infection or any immunosuppressive disorder, including HIV infection.
  3. Significant liver dysfunction.
  4. Prior liver biopsy showing significant fibrosis.
  5. Evidence of any bleeding disorder not related to hemophilia A.
  6. Platelet count of < 100 x 10^9/L.
  7. Creatinine ≥ 1.5 mg/dL.
  8. Liver cirrhosis of any etiology as assessed by liver ultrasound.
  9. Chronic or active hepatitis B.
  10. Active Hepatitis C.
  11. Active malignancy, except non-melanoma skin cancer.
  12. History of hepatic malignancy.
  13. History of arterial or venous thromboembolic events.
  14. Known inherited or acquired thrombophilia, including conditions associated with increased thromboembolic risk, such as atrial fibrillation.

Sites / Locations

  • Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center
  • UC Davis Hemophilia Treatment Center
  • University of California San Diego, Hematology and Oncology, Hemophilia &Thrombosis Treatment Center
  • UCSF Medical Center
  • University of Colorado
  • St. Joseph's Children's Hospital, Center for Bleeding and Clotting Disorders
  • Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Hematology
  • James Graham Brown Cancer Center
  • University of Michigan, Pediatric Hematology and Oncology
  • Wayne State University, Detroit Medical Center
  • University of Minnesota
  • Washington University School of Medicine, Department of Pediatrics, Division of Hematology/Oncology
  • UNC Hemophilia and Thrombosis Center
  • Nationwide Children's Hospital
  • The Royal Adelaide Hospital (RAH)
  • Royal Brisbane and Women's Hospital
  • Alfred Hospital
  • Fiona Stanley Hospital
  • Royal Prince Alfred Hospital
  • University Hospital Leuven
  • Campinas Estadual University (UNICAMP) / Campinas Hemocentro / Hematologia E Hemoterapia Center
  • Parana's Hematology And Hemotherapy Center (HEMEPAR)
  • Arthur De Siqueira Cavalcanti Hematology State Institute
  • Sao Paulo University Clinical Hospital
  • Holy Spirit Hematology and Hemotherapy Center
  • Regional University Hospital of Lille (CHRU de Lille)
  • Hopital de la Timone Marseille - Assistance Publique des Hopitaux de Marseille
  • Vivantes Clinic im Friedrichshain- Landsberger Allee
  • University Clinic Bonn
  • Chaim Sheba Medical Center
  • Maggiore Polyclinic Hospital, IRCCS Ca' Granda, Center for Hemophilia and Thrombosis Angelo Bianchi Bonomi
  • Department of Pediatrics, Kyung Hee University Hospital at Gangdong
  • Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center
  • Hospital Teresa Herrera
  • University Hospital Virgen del Rocio (HUVR)
  • Changhua Christian Hospital
  • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung Veterans General Hospital
  • National Taiwan University Hospital
  • Tri-Service General Hospital
  • Queen Elizabeth Hospital
  • Addenbrookes Hospital
  • Glasgow Royal Infirmary, Department of Hematology
  • Barts and The London School of Medicine and Dentistry, Haemophilia Centre
  • Hammersmith
  • St Thomas' Hospital
  • Churchill Hospital, Oxford Hemophilia and Thrombosis Center
  • University Hospital Southampton NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

valoctocogene roxaparvovec Open Label

Arm Description

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

Outcomes

Primary Outcome Measures

Change from baseline in the median FVIII activity, as measured by chromogenic substrate assay, during Weeks 49-52 post-BMN 270 infusion

Secondary Outcome Measures

Change from baseline in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy from Week 5 to last visit by data cut-off
Change from baseline in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment from Week 5 to last visit by data cut-off

Full Information

First Posted
November 27, 2017
Last Updated
December 21, 2022
Sponsor
BioMarin Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT03370913
Brief Title
Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270-301)
Acronym
BMN 270-301
Official Title
A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII Infusions
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 19, 2017 (Actual)
Primary Completion Date
November 16, 2020 (Actual)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This Phase III clinical study will assess the efficacy of BMN 270 defined as FVIII activity, during weeks 49-52 following intravenous infusion of BMN 270 and assess the impact of BMN 270 on usage of exogenous FVIII replacement therapy and the number of bleeding episodes from week 5 to last visit by data cutoff.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
134 (Actual)

8. Arms, Groups, and Interventions

Arm Title
valoctocogene roxaparvovec Open Label
Arm Type
Experimental
Arm Description
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg
Intervention Type
Biological
Intervention Name(s)
valoctocogene roxaparvovec
Other Intervention Name(s)
BMN 270
Intervention Description
Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A
Primary Outcome Measure Information:
Title
Change from baseline in the median FVIII activity, as measured by chromogenic substrate assay, during Weeks 49-52 post-BMN 270 infusion
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Change from baseline in the annualized utilization (IU/kg) of exogenous FVIII replacement therapy from Week 5 to last visit by data cut-off
Time Frame
52 weeks
Title
Change from baseline in the annualized number of bleeding episodes requiring exogenous FVIII replacement treatment from Week 5 to last visit by data cut-off
Time Frame
52 weeks
Other Pre-specified Outcome Measures:
Title
Percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.03 in the first 52 weeks following valoctocogene roxaparvovec infusion
Time Frame
52 weeks
Title
Percentage of participants with treatment-related adverse events, as assessed by de novo development of FVIII inhibitors in the first 52 weeks following valoctocogene roxaparvovec infusion
Time Frame
52 weeks
Title
Percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.03 during years 2-5 following valoctocogene roxaparvovec infusion
Time Frame
5 years
Title
Percentage of participants with treatment-related adverse events, as assessed by de novo development of FVIII inhibitors during years 2-5 following valoctocogene roxaparvovec infusion
Time Frame
5 years

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Biological males only
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Detectable pre-existing antibodies to the AAV5 capsid. Any evidence of active infection or any immunosuppressive disorder, including HIV infection. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor, MD
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
Facility Name
Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90007-2664
Country
United States
Facility Name
UC Davis Hemophilia Treatment Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of California San Diego, Hematology and Oncology, Hemophilia &Thrombosis Treatment Center
City
San Diego
State/Province
California
ZIP/Postal Code
92122
Country
United States
Facility Name
UCSF Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0106
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
St. Joseph's Children's Hospital, Center for Bleeding and Clotting Disorders
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Hematology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2605
Country
United States
Facility Name
James Graham Brown Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Michigan, Pediatric Hematology and Oncology
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5718
Country
United States
Facility Name
Wayne State University, Detroit Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine, Department of Pediatrics, Division of Hematology/Oncology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1093
Country
United States
Facility Name
UNC Hemophilia and Thrombosis Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
The Royal Adelaide Hospital (RAH)
City
Adelaide
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Perth
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Sydney
Country
Australia
Facility Name
University Hospital Leuven
City
Leuven
Country
Belgium
Facility Name
Campinas Estadual University (UNICAMP) / Campinas Hemocentro / Hematologia E Hemoterapia Center
City
Campinas
Country
Brazil
Facility Name
Parana's Hematology And Hemotherapy Center (HEMEPAR)
City
Curitiba
Country
Brazil
Facility Name
Arthur De Siqueira Cavalcanti Hematology State Institute
City
Rio De Janeiro
Country
Brazil
Facility Name
Sao Paulo University Clinical Hospital
City
São Paulo
Country
Brazil
Facility Name
Holy Spirit Hematology and Hemotherapy Center
City
Vitória
Country
Brazil
Facility Name
Regional University Hospital of Lille (CHRU de Lille)
City
Lille
Country
France
Facility Name
Hopital de la Timone Marseille - Assistance Publique des Hopitaux de Marseille
City
Marseille
Country
France
Facility Name
Vivantes Clinic im Friedrichshain- Landsberger Allee
City
Berlin
Country
Germany
Facility Name
University Clinic Bonn
City
Bonn
Country
Germany
Facility Name
Chaim Sheba Medical Center
City
Ramat Gan
Country
Israel
Facility Name
Maggiore Polyclinic Hospital, IRCCS Ca' Granda, Center for Hemophilia and Thrombosis Angelo Bianchi Bonomi
City
Milan
Country
Italy
Facility Name
Department of Pediatrics, Kyung Hee University Hospital at Gangdong
City
Seoul
Country
Korea, Republic of
Facility Name
Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center
City
Johannesburg
Country
South Africa
Facility Name
Hospital Teresa Herrera
City
A Coruna
Country
Spain
Facility Name
University Hospital Virgen del Rocio (HUVR)
City
Seville
Country
Spain
Facility Name
Changhua Christian Hospital
City
Changhua
Country
Taiwan
Facility Name
Kaohsiung Medical University Chung-Ho Memorial Hospital
City
Kaohsiung
Country
Taiwan
Facility Name
Taichung Veterans General Hospital
City
Taichung
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Facility Name
Tri-Service General Hospital
City
Taipei
Country
Taiwan
Facility Name
Queen Elizabeth Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Addenbrookes Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Glasgow Royal Infirmary, Department of Hematology
City
Glasgow
Country
United Kingdom
Facility Name
Barts and The London School of Medicine and Dentistry, Haemophilia Centre
City
London
Country
United Kingdom
Facility Name
Hammersmith
City
London
Country
United Kingdom
Facility Name
St Thomas' Hospital
City
London
Country
United Kingdom
Facility Name
Churchill Hospital, Oxford Hemophilia and Thrombosis Center
City
Oxford
Country
United Kingdom
Facility Name
University Hospital Southampton NHS Foundation Trust
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35879931
Citation
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.
Results Reference
derived
PubMed Identifier
35294811
Citation
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.
Results Reference
derived
PubMed Identifier
32915950
Citation
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.
Results Reference
derived

Learn more about this trial

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

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