Gene Therapy Study in Severe Haemophilia A Patients (270-201)

NCT ID: NCT02576795

Last Updated: 2025-04-10

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-28

Study Completion Date

2024-02-14

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study is being conducted by BioMarin Pharmaceutical Inc. as an open label, dose escalation study in order to determine the safety and efficacy of valoctocogene roxaparvovec (an Adenovirus-Associated Virus based gene therapy vector in participants with severe haemophilia A.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Severe Haemophilia A

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

valoctocogene roxaparvovec

Single administration of valoctocogene roxaparvovec at escalating doses.

Group Type EXPERIMENTAL

valoctocogene roxaparvovec

Intervention Type BIOLOGICAL

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

valoctocogene roxaparvovec

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

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

BMN 270

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Males 18 years or older with established severe Haemophilia A (endogenous FVIII level ≤1 IU/dL) as evidenced by their medical history.
2. Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs)
3. Greater than or equal to 12 bleeding episodes for patients on on-demand FVIII replacement therapy over the previous 12 months. Does not apply to patients on prophylaxis
4. No history of inhibitor, and results from a modified Nijmegen Bethesda assay of less than 0.6 Bethesda Units (BU) 2 consecutive occasions at least one week apart within the past 12 months
5. Sexually active patients must be willing to use an acceptable method of contraception.

Exclusion Criteria

1. Detectable pre-existing immunity to the AAV5 capsid as measured by adeno-associated virus 5 (AAV5) transduction inhibition (TI) or AAV5 total antibodies
2. Any evidence of immunosuppressive disorder or active chronic infection including hepatis B, hepatitis C, HIV
3. Significant liver dysfunction as defined by abnormal elevation ofliver function tests, or for patients who have undergone liver imaging or biopsy and found to have evidence of grade 3 or higher fibrosis
4. Evidence of any bleeding disorder not related to haemophilia A
5. 12\. Treatment with any investigational product within 30 days prior to the end of the screening period, or any previous exposure to any gene transfer therapy
6. Any disease or condition that per the physician's discretion would prevent the patient from fully complying with the requirements of the study including possible corticosteroid treatment outlined in the protocol. The physician may exclude patients unwilling or unable to agree on not using alcohol for the 16-week period following the viral infusion.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Queen Elizabeth Hospital Birmingham

Birmingham, , United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

St. Thomas' Hospital

London, , United Kingdom

Site Status

The Royal London Hospital

London, , United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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)

Symington E, Rangarajan S, Lester W, Madan B, Pierce GF, Raheja P, Millar C, Osmond D, Li M, Robinson TM. Valoctocogene roxaparvovec gene therapy provides durable haemostatic control for up to 7 years for haemophilia A. Haemophilia. 2024 Sep;30(5):1138-1147. doi: 10.1111/hae.15071. Epub 2024 Jul 8.

Reference Type DERIVED
PMID: 38975624 (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)

Fong S, Yates B, Sihn CR, Mattis AN, Mitchell N, Liu S, Russell CB, Kim B, Lawal A, Rangarajan S, Lester W, Bunting S, Pierce GF, Pasi KJ, Wong WY. Interindividual variability in transgene mRNA and protein production following adeno-associated virus gene therapy for hemophilia A. Nat Med. 2022 Apr;28(4):789-797. doi: 10.1038/s41591-022-01751-0. Epub 2022 Apr 11.

Reference Type DERIVED
PMID: 35411075 (View on PubMed)

Pasi KJ, Laffan M, Rangarajan S, Robinson TM, Mitchell N, Lester W, Symington E, Madan B, Yang X, Kim B, Pierce GF, Wong WY. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 2021 Nov;27(6):947-956. doi: 10.1111/hae.14391. Epub 2021 Aug 11.

Reference Type DERIVED
PMID: 34378280 (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)

Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, Laffan M, Russell CB, Li M, Pierce GF, Wong WY. Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A. N Engl J Med. 2020 Jan 2;382(1):29-40. doi: 10.1056/NEJMoa1908490.

Reference Type DERIVED
PMID: 31893514 (View on PubMed)

Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, Yu H, Vettermann C, Pierce GF, Wong WY, Pasi KJ. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017 Dec 28;377(26):2519-2530. doi: 10.1056/NEJMoa1708483. Epub 2017 Dec 9.

Reference Type DERIVED
PMID: 29224506 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2014-003880-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BMN 270-201

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

A Gene Therapy Study for Hemophilia B
NCT02484092 COMPLETED PHASE2
BAX 855 Dose-Escalation Safety Study
NCT01599819 COMPLETED PHASE1
BAX 855 Continuation
NCT01945593 COMPLETED PHASE3
Lentiviral FVIII Gene Therapy
NCT03217032 UNKNOWN PHASE1