NCT04684940: GENEr8-INH

A Phase 1/2 Safety, Tolerability, and Efficacy Study of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Active or Prior Inhibitors

Active, enrolled Phase 1/Phase 2 Last updated 10 July 2025

What this trial tests

Phase 1/Phase 2 trial testing Valoctocogene roxaparvovec in Hemophilia A With Inhibitor in 10 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

10 December 2020

Primary endpoint
1 April 2029

1 April 2029

Quick facts

Lead sponsor	BioMarin Pharmaceutical
Phase	Phase 1/Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	10 December 2020
Primary completion	1 April 2029
Estimated completion	1 April 2029
Sites	9 locations across United States, Brazil, Israel, South Korea, Taiwan, Turkey (Türkiye)

Drugs / interventions tested

• Valoctocogene roxaparvovec (VALOCTOCOGENE ROXAPARVOVEC) — full drug profile →

Conditions studied

• Hemophilia A With Inhibitor — all drugs for Hemophilia A With Inhibitor →
• Hemophilia A With Anti Factor VIII — all drugs for Hemophilia A With Anti Factor VIII →

Sponsor

BioMarin Pharmaceutical — full company profile →

Who can join

18 and older, male only, with Hemophilia A With Inhibitor or Hemophilia A With Anti Factor VIII. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Number of participants with treatment-related adverse events, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 after administration of BMN 270.
  Time frame: 60 months

Sponsor's own description

This Phase I/II clinical study will evaluate the safety and efficacy of valoctocogene roxaparvovec in patients with severe haemophilia A and inhibitors to FVIII. Part A of the study will involve subjects who have active inhibitors to FVIII, and Part B involving subjects with a prior history of inhibitors.

Publications & conference data

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

1. 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
2. Gene therapy for hemophilia.
   Nathwani AC. · · 2022 · cited 74× · PMID 36485127 · DOI 10.1182/hematology.2022000388
3. Emerging Immunogenicity and Genotoxicity Considerations of Adeno-Associated Virus Vector Gene Therapy for Hemophilia.
   Monahan PE, Négrier C, Tarantino M, Valentino LA, et al · · 2021 · cited 62× · PMID 34199563 · DOI 10.3390/jcm10112471
4. The intersection of vector biology, gene therapy, and hemophilia.
   Lisowski L, Staber JM, Wright JF, Valentino LA. · · 2021 · cited 16× · PMID 34485808 · DOI 10.1002/rth2.12586
5. Evaluating Gene Therapy as a Potential Paradigm Shift in Treating Severe Hemophilia.
   Thornburg CD, Simmons DH, von Drygalski A. · · 2023 · cited 15× · PMID 37490225 · DOI 10.1007/s40259-023-00615-4
6. Coagulation factor VIII: biological basis of emerging hemophilia A therapies.
   Samelson-Jones BJ, Doshi BS, George LA. · · 2024 · cited 12× · PMID 39088776 · DOI 10.1182/blood.2023023275
7. Immune tolerance induction by hepatic gene transfer: First-in-human evidence.
   Kaczmarek R, Samelson-Jones BJ, Herzog RW. · · 2024 · cited 12× · PMID 38518767 · DOI 10.1016/j.ymthe.2024.03.016
8. Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.
   Yin L, He H, Zhang H, Shang Y, et al · · 2025 · cited 9× · PMID 40536197 · DOI 10.1002/jmv.70447