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NCT03520712: GENEr8-AAV5+

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

Terminated Phase 1, PHASE2 Results posted Last updated 22 August 2025
What this trial tests

Phase 1, PHASE2 trial testing Valoctocogene Roxaparvovec in Hemophilia A in 3 participants. Terminated before completion.

Timeline
24 April 2018
Primary endpoint
7 August 2024
7 August 2024

Quick facts

Lead sponsorBioMarin Pharmaceutical
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment3
Start date24 April 2018
Primary completion7 August 2024
Estimated completion7 August 2024
Sites9 locations across Taiwan, South Africa, United Kingdom, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

BioMarin Pharmaceutical — full company profile →

Who can join

18 and older, male only, with Hemophilia A or Gene Therapy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment Emergent Adverse Events Primary · Up to 5 years post-infusion.

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

Participants with any AE
GroupValue95% CI
BMN 270 6E13 vg/kg3
Participants with any SAE
GroupValue95% CI
BMN 270 6E13 vg/kg1
Participants with any treatment-related AE
GroupValue95% CI
BMN 270 6E13 vg/kg3
Treatment-related SAEs
GroupValue95% CI
BMN 270 6E13 vg/kg1
Participants with any AE of Grade >= 3
GroupValue95% CI
BMN 270 6E13 vg/kg1
AEs leading to dose adjustment during infusion
GroupValue95% CI
BMN 270 6E13 vg/kg0
AEs leading to dose interruption during infusion
GroupValue95% CI
BMN 270 6E13 vg/kg0
AEs leading to study drug discontinuation
GroupValue95% CI
BMN 270 6E13 vg/kg0
Number of Participant With FVIII Activity >= 5 IU/dL at Week 26. Using Chromogenic Substrate Assay (CSA). Secondary · 26 weeks

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).

GroupValue95% CI
BMN 270 6E13 vg/kg1
BMN 270 6E13 vg/kg2
Mean Annualized Factor VIII Utilization During Week 5 and Beyond Secondary · Week 5 and Beyond (Follow-Up, up to 1782 Days)

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

GroupValue95% CI
BMN 270 6E13 vg/kg661.1± 912.92
Mean Annualized Factor VIII Infusion Rate During Week 5 and Beyond Secondary · Week 5 and Beyond (Follow-Up, up to 1782 Days)

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

GroupValue95% CI
BMN 270 6E13 vg/kg21.9± 30.61
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. Secondary · Week 5 and Beyond (Follow-Up, up to 1782 Days)

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

GroupValue95% CI
BMN 270 6E13 vg/kg3
BMN 270 6E13 vg/kg0

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 5 years post-infusion.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BMN 270 6E13 vg/kg
Serious: 1/3 (33%)
Deaths: 0/3

Serious adverse events (1 terms)

ReactionSystemBMN 270 6E13 vg/kg
HypersensitivityImmune system disorders
Other adverse events (16 terms — click to expand)

ReactionSystemBMN 270 6E13 vg/kg
Alanine aminotransferase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
HypersensitivityImmune system disorders
Animal scratchInjury, poisoning and procedural complications
Face injuryInjury, poisoning and procedural complications
OnychomycosisInfections and infestations
Tendon disorderMusculoskeletal and connective tissue disorders
Covid-19Infections and infestations
Conjunctivitis viralInfections and infestations
Limb injuryInjury, poisoning and procedural complications
Skin abrasionInjury, poisoning and procedural complications
Muscle injuryInjury, poisoning and procedural complications
Gastrointestinal infectionInfections and infestations
HerniaGeneral disorders
Thermal burnsInjury, poisoning and procedural complications
InfluenzaInfections and infestations

Most-reported serious reactions: Hypersensitivity.

Data from ClinicalTrials.gov NCT03520712 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current Clinical Applications of In Vivo Gene Therapy with AAVs.
    Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, et al · · 2021 · cited 544× · PMID 33309881 · DOI 10.1016/j.ymthe.2020.12.007
  2. Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings.
    Au HKE, Isalan M, Mielcarek M. · · 2021 · cited 208× · PMID 35223884 · DOI 10.3389/fmed.2021.809118
  3. Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders.
    Shahryari A, Saghaeian Jazi M, Mohammadi S, Razavi Nikoo H, et al · · 2019 · cited 168× · PMID 31608113 · DOI 10.3389/fgene.2019.00868
  4. Update on clinical gene therapy for hemophilia.
    Perrin GQ, Herzog RW, Markusic DM. · · 2019 · cited 128× · PMID 30559260 · DOI 10.1182/blood-2018-07-820720
  5. Durability of transgene expression after rAAV gene therapy.
    Muhuri M, Levy DI, Schulz M, McCarty D, et al · · 2022 · cited 94× · PMID 35283274 · DOI 10.1016/j.ymthe.2022.03.004
  6. Global Seroprevalence of Pre-existing Immunity Against AAV5 and Other AAV Serotypes in People with Hemophilia A.
    Klamroth R, Hayes G, Andreeva T, Gregg K, et al · · 2022 · cited 90× · PMID 35156839 · DOI 10.1089/hum.2021.287
  7. Testing preexisting antibodies prior to AAV gene transfer therapy: rationale, lessons and future considerations.
    Mendell JR, Connolly AM, Lehman KJ, Griffin DA, et al · · 2022 · cited 87× · PMID 35356756 · DOI 10.1016/j.omtm.2022.02.011
  8. A Molecular Revolution in the Treatment of Hemophilia.
    Butterfield JSS, Hege KM, Herzog RW, Kaczmarek R. · · 2020 · cited 76× · PMID 31843450 · DOI 10.1016/j.ymthe.2019.11.006

Verify or expand the search:

Other trials of Valoctocogene Roxaparvovec

Trials testing the same drug.

Other recruiting trials for Hemophilia A

Currently open trials in the same condition.

Other BioMarin Pharmaceutical trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03520712.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing