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TerminatedNCT03520712GENEr8-AAV5+Updated Aug 22, 2025Results posted

Gene Therapy Study in Severe Hemophilia A Patients With Antibodies Against AAV5

A Phase 1/2 interventional study of Valoctocogene Roxaparvovec in Hemophilia A, Gene Therapy and Clotting Disorders, sponsored by BioMarin Pharmaceutical. Terminated at 9 sites in 4 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-22.

Sponsored by BioMarin Pharmaceutical · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Early rollover into long-term extension study
Phase
Phase 1/2
Study type
Interventional
Enrollment
3
Allocation
Not applicable
Ages
18 Years and older
Sex
Male
01

Study summary

This study is being conducted by BioMarin Pharmaceutical Inc. as an open label, single dose study to determine the safety of valoctocogene roxaparvovec (an Adenovirus-Associated Virus (AAV) based gene therapy vector) in severe Hemophilia A patients with pre-existing antibodies against AAV5.

02

Conditions studied

  • Hemophilia A
  • Gene Therapy
  • Clotting Disorders
  • Blood Disorder

Keywords

  • Hemophilia A
  • Blood Coagulation Disorders, Inherited
  • Blood Coagulation Disorders
  • Hematologic Diseases
  • Coagulation Protein Disorders
  • Hemorrhagic Disorders
  • Genetic Diseases, Inborn
  • Factor VIII
  • Coagulants
  • AAV5 antibodies
03

In context

Hemophilia A

866 studies on the registry are indexed under Hemophilia A; 137 are open to participants now.

This study's enrollment of 3 is below the median of 28 across 512 interventional studies indexed under Hemophilia A.

Browse Hemophilia A studies →

Lead sponsor

BioMarin Pharmaceutical is the lead sponsor of 110 studies on the registry; 13 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 12 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

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. Detectable pre-existing antibodies against the AAV5 vector capsid as measured by AAV5 total antibody ELISA.
  3. Subject must have been on prophylactic FVIII replacement therapy for at least 12 months prior to study entry.
  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) (or less than 1.0 BU for laboratories with a historical lower sensitivity cutoff for inhibitor detection of 1.0 BU) on 2 consecutive occasions at least one week apart within the past 12 months (at least one of which should be tested at the central laboratory).
  5. Sexually active participants must agree to use an acceptable method of effective contraception. Participants must agree to contraception use for at least 12 weeks post-infusion.

Exclusion criteria

Exclusion Criteria:

  1. Any evidence of active infection including COVID-19, or any immunosuppressive disorder, except for HIV infection. HIV positive patients who meet all other eligibility criteria may be included if they have a CD4 count > 200/mm3 and an undetectable viral load (unquantifiable viral load as defined as less than the limit of quantification by the testing laboratory's assay is permitted) while receiving an antiretroviral therapy (ART) regimen that does not contain efavirenz or another potentially hepatotoxic ART.
  2. Evidence of liver dysfunction as assessed by liver tests and most recent, prior FibroScan or liver biopsy showing significant fibrosis of 3 or 4 as rated on a scale of 0-4 on the Batts-Ludwig (Batts 1995) or METAVIR (Bedossa 1996) scoring systems, or an equivalent grade of fibrosis if an alternative scale is used.
  3. Chronic or active hepatitis B or C as evidenced by testing at screening.
  4. Active malignancy, except non-melanoma skin cancer, or history of hepatic malignancy.
  5. Any condition that, in the opinion of the investigator or Sponsor would prevent the patient from fully complying with the requirements of the study (including corticosteroid treatment and/or use of alternative immunosuppressive agents outlined in the protocol) and/or would impact or interfere with evaluation and interpretation of subject safety or efficacy result.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
3 participants (actual)

Study arms

  • Experimental
    valoctocogene roxaparvovec Open Label

    Single administration of BMN270 at a dose of 6E13 vg/kg

    Biological: Valoctocogene Roxaparvovec

Interventions

  • BiologicalValoctocogene Roxaparvovec

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

    Also known as: BMN 270

06

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events

    A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.

    Time frame: Up to 5 years post-infusion.

Secondary outcomes

  1. Number of Participant With FVIII Activity >= 5 IU/dL at Week 26. Using Chromogenic Substrate Assay (CSA).

    Prior to BMN270 infusion, screening FVIII activity levels where participants had not received exogenous FVIII within 72 hours of assessment were below the lower limit of quantitation (LLOQ) as measured by CSA (LLOQ = 0.015 IU/mL).

    Time frame: 26 weeks

  2. Mean Annualized Factor VIII Utilization During Week 5 and Beyond

    The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25

    Time frame: Week 5 and Beyond (Follow-Up, up to 1782 Days)

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

    Annualized FVIII replacement infusion rate=(number of FVFIII replacement infusions during calculation period/sum(follow-up days) of the period)\*365.25

    Time frame: Week 5 and Beyond (Follow-Up, up to 1782 Days)

  4. Number of Participants Showed Reduction in the ABR Post-BMN 270 Infusion. Impact of BMN 270 on the Number of Bleeding Episodes Requiring Exogenous FVIII Therapy.

    Annualized bleeding rate (ABR) (counts/yr.)=Number of bleeding episodes during calculation period/Total number of days during the calculation period ×365.25

    Time frame: Week 5 and Beyond (Follow-Up, up to 1782 Days)

07

Results

Posted Aug 22, 2025
Limitations and caveats
In accordance with the study enrollment stopping criteria in the 270-203 study protocol and the Data Monitoring Committee (DMC) recommendation, decided to terminate 270-203, since 2 of the 3 participants in Cohort 1 (AAV5 TAb≤500) had FVIII activity 5IU/dL after a minimum of 6 weeks post-BMN 270 infusion. The last participant visit, and 270-203 termination, occurred on 07 August 2024.

Participant flow

This study was conducted by 2 principal investigators at 2 study centers in 2 countries (South Africa and United Kingdom). Nine investigational sites were activated, 2 subjects in South Africa and 1 subject in the United Kingdom were enrolled in the study.

Participant flow — Overall Study
MilestoneBMN 270 6E13 vg/kg
Started3
Completed1
Not completed2
Withdrew: Early termination of the study by sponsor2

Outcome measures

PrimaryNumber of Participants With Treatment Emergent Adverse Events

A treatment-emergent adverse event (TEAE) is defined as any AE that newly appeared or worsened in severity following initiation of investigational product administration.

Time frame:
Up to 5 years post-infusion.
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events
ParticipantsBMN 270 6E13 vg/kg
Participants with any AE3
Participants with any SAE1
Participants with any treatment-related AE3
Treatment-related SAEs1
Participants with any AE of Grade >= 31
AEs leading to dose adjustment during infusion0
AEs leading to dose interruption during infusion0
AEs leading to study drug discontinuation0
Participants who died0
SecondaryNumber of Participant With FVIII Activity >= 5 IU/dL at Week 26. Using Chromogenic Substrate Assay (CSA).

Prior to BMN270 infusion, screening FVIII activity levels where participants had not received exogenous FVIII within 72 hours of assessment were below the lower limit of quantitation (LLOQ) as measured by CSA (LLOQ = 0.015 IU/mL).

Time frame:
26 weeks
Reported as:
Count of participants · Participants
Number of Participant With FVIII Activity >= 5 IU/dL at Week 26. Using Chromogenic Substrate Assay (CSA).
ParticipantsBMN 270 6E13 vg/kg
Participant with FVIII activity >= 5 IU/dL1
Participant with FVIII activity < 5 IU/dL2
SecondaryMean Annualized Factor VIII Utilization During Week 5 and Beyond

The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25

Time frame:
Week 5 and Beyond (Follow-Up, up to 1782 Days)
Reported as:
Mean · IU/kg/yr
Mean Annualized Factor VIII Utilization During Week 5 and Beyond
IU/kg/yrBMN 270 6E13 vg/kg
Mean Annualized Factor VIII Utilization During Week 5 and Beyond661.1 ± 912.92
SecondaryMean Annualized Factor VIII Infusion Rate During Week 5 and Beyond

Annualized FVIII replacement infusion rate=(number of FVFIII replacement infusions during calculation period/sum(follow-up days) of the period)\*365.25

Time frame:
Week 5 and Beyond (Follow-Up, up to 1782 Days)
Reported as:
Mean · ml/min
Mean Annualized Factor VIII Infusion Rate During Week 5 and Beyond
ml/minBMN 270 6E13 vg/kg
Mean Annualized Factor VIII Infusion Rate During Week 5 and Beyond21.9 ± 30.61
SecondaryNumber of Participants Showed Reduction in the ABR Post-BMN 270 Infusion. Impact of BMN 270 on the Number of Bleeding Episodes Requiring Exogenous FVIII Therapy.

Annualized bleeding rate (ABR) (counts/yr.)=Number of bleeding episodes during calculation period/Total number of days during the calculation period ×365.25

Time frame:
Week 5 and Beyond (Follow-Up, up to 1782 Days)
Reported as:
Count of participants · Participants
Number of Participants Showed Reduction in the ABR Post-BMN 270 Infusion. Impact of BMN 270 on the Number of Bleeding Episodes Requiring Exogenous FVIII Therapy.
ParticipantsBMN 270 6E13 vg/kg
Participants showed reduction in the ABR post-BMN 270 infusion3
Participants who did not show reduction in the ABR post-BMN 270 infusion0

Adverse events

Collected over up to 5 years post-infusion.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
BMN 270 6E13 vg/kg0/3 (0%)1/3 (33.3%)3/3 (100%)
Most frequent serious events
Most frequent serious events
EventBMN 270 6E13 vg/kg
HypersensitivityImmune system disorders1/3
Most frequent other events
Showing 10 of 16
Most frequent other events
EventBMN 270 6E13 vg/kg
Alanine aminotransferase increasedInvestigations2/3
ArthralgiaMusculoskeletal and connective tissue disorders1/3
HypersensitivityImmune system disorders1/3
Animal scratchInjury, poisoning and procedural complications1/3
Face injuryInjury, poisoning and procedural complications1/3
OnychomycosisInfections and infestations1/3
Tendon disorderMusculoskeletal and connective tissue disorders1/3
Covid-19Infections and infestations1/3
Conjunctivitis viralInfections and infestations1/3
Limb injuryInjury, poisoning and procedural complications1/3

Baseline characteristics

The intention-to-treat (ITT) population was comprised of all participants who have received the BMN 270 infusion.

Age, Categorical
Age, Categorical(Participants)BMN 270 6E13 vg/kg
<=18 years0
Between 18 and 65 years3
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)BMN 270 6E13 vg/kg
Female0
Male3
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)BMN 270 6E13 vg/kg
White Non-Hispanic2
Black or African American1
Region of Enrollment
Region of Enrollment(participants)BMN 270 6E13 vg/kg
United Kingdom1
South Africa2
08

Study locations

9 sites
  • Charlotte Maxeke Johannesburg Academic Hospital, Hemophilia Comprehensive Care Center
    Johannesburg, South Africa
  • Kyung Hee University Hospital at Gangdong
    Seoul, South Korea
  • Severance Hospital, Yonsei University Health System
    Seoul, South Korea
  • 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
  • Royal Free Hospital
    London, United Kingdom
  • University Hospital Southampton NHS Foundation Trust
    Southampton, United Kingdom
09

References and documents

Study documents

  • Study protocol · Jul 7, 2022
  • Statistical analysis plan · Mar 26, 2024

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 22, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03520712
Lead sponsor
BioMarin Pharmaceutical
Responsible party
Sponsor
First posted
May 11, 2018
Start date
Apr 24, 2018
Primary completion
Aug 7, 2024
Completion
Aug 7, 2024
Results posted
Aug 22, 2025
Last update
Aug 22, 2025

Study contacts

Medical Director, MD
study director · BioMarin Pharmaceutical

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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