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Severe Haemophilia APhase 1/2NCT02576795

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

A Phase 1/2 study testing valoctocogene roxaparvovec in people with Severe Haemophilia A, run by BioMarin Pharmaceutical at 5 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Severe Haemophilia A
What is being tested?
valoctocogene roxaparvovec
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
5 sitesUnited Kingdom
Study dates
28 Sep 2015to 14 Feb 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males 18 years or older with established severe Haemophilia A (endogenous FVIII level ≤1 IU/dL) as evidenced by their medical history.
  • Treated/exposed to FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs)
  • 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
  • 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
  • Sexually active patients must be willing to use an acceptable method of contraception.

Who cannot join

  • Detectable pre-existing immunity to the AAV5 capsid as measured by adeno-associated virus 5 (AAV5) transduction inhibition (TI) or AAV5 total antibodies
  • Any evidence of immunosuppressive disorder or active chronic infection including hepatis B, hepatitis C, HIV
  • 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
  • Evidence of any bleeding disorder not related to haemophilia A
  • 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
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United Kingdom5 sites
  • Queen Elizabeth Hospital Birmingham

    Birmingham

  • Addenbrooke's Hospital

    Cambridge

  • St. Thomas' Hospital

    London

  • The Royal London Hospital

    London

  • University Hospital Southampton NHS Foundation Trust

    Southampton

Other trials in United Kingdom

About this study

Official title: A Phase 1/2, Dose-Escalation, Safety, Tolerability and Efficacy Study of Valoctocogene Roxaparvovec, an Adenovirus-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Patients With Severe Haemophilia A

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.

Being tested
valoctocogene roxaparvovec
Keywords
Haemophilia A, 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, AAV5 vector
Medical subject headings
Hemophilia A, Hemostatic Disorders, Hematologic Diseases, Blood Coagulation Disorders, Inherited, Blood Coagulation Disorders, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • valoctocogene roxaparvovecBiological

    Also called BMN 270

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

Study groups in NCT02576795
Study groupRoleWhat they receive
valoctocogene roxaparvovecExperimentalSingle administration of valoctocogene roxaparvovec at escalating doses.
Receives: Biological: valoctocogene roxaparvovec

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment Emergent Adverse Events

    Adverse events (AEs) with onset or worsening after the investigational product were included. Participants with more than one AE of the same category were counted only once for that category.

    Serious adverse event (SAE)

    Measured: Approximately up to 7 years after dosing

  2. Number of Participant With Median FVIII Activity Levels >= 5 IU/dL Using Chromogenic Substrate Assay (CSA)

    Responder/Non responder status, where a responder was defined as a participant with median FVIII activity of >= 5 IU/dL during Week 13-16 post-BMN 270 infusion

    Measured: Week 13-16 post-BMN 270 infusion

  3. Median FVIII Activity as Measured by Chromogenic Substrate Assay During Week 13-16 Post-BMN 270 Infusion

    Values for FVIII activity were excluded from analysis if obtained within 72 hours since the last infusion of exogenous FVIII replacement therapy

    FVIII activity levels below the Lower limit of quantitation (LLOQ) will be imputed with 0 IU/dL

    Q1: 25% Percentile; Q3: 75% Percentile

    Measured: Week 13-16 post-BMN 270 infusion

Secondary outcomes (3)
  1. Annualized Bleeding Rate Requiring Exogenous Factor VIII Replacement Treatment During Week 5 and Beyond

    ABR= [Number of bleeding episodes during calculation period] / [Total number of days during the calculation period] ×365.25

    A bleeding episode (treated) was defined as a bleed or symptoms associated with the development of a bleed (or multiple bleeds occurring in the same day) requiring FVIII replacement treatment within 72 hours of the start of the bleed.

    The baseline values for the secondary efficacy endpoints were based on the historical data prior to study enrollment.

    Annualized bleeding rate (ABR)

    Measured: Week 5 and Beyond (Approximately 7 years post Infusion)

  2. Annualized Factor VIII Utilization During Week 5 and Beyond

    Annualized FVIII use (IU/kg/yr.) =[Sum of FVIII use (IU/kg) during calculation period] / [Total number of days during the calculation period] ×365.25

    Measured: Week 5 and Beyond (Approximately 7 years post Infusion)

  3. Annualized Factor VIII Infusion Rate During Week 5 and Beyond

    Annualized FVIII infusion rate (count/yr.) = [Number of FVIII replacement infusions during calculation period] / [Total number of days during the calculation period] ×365.25

    Measured: Week 5 and Beyond (Approximately 7 years post Infusion)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2015 (estimated)
  2. Study start28 Sep 2015
  3. Primary completion14 Feb 2024
  4. Study completion14 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02576795
Sponsor's protocol ID
BMN 270-201
Other IDs
2014-003880-38, 2014
Status last verified
Mar 2025
First submitted
5 Oct 2015
Last updated
10 Apr 2025
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40986187
  • 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.

    PubMed 38975624
  • 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.

    PubMed 35879931
  • 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.

    PubMed 35411075
  • 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.

    PubMed 34378280
  • 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.

    PubMed 32915950
  • 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.

    PubMed 31893514
  • 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.

    PubMed 29224506

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing valoctocogene roxaparvovec in people with Severe Haemophilia A, run by BioMarin Pharmaceutical at 5 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Emergent Adverse Events (time frame: Approximately up to 7 years after dosing). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02576795, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2025.

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