A Phase 1/2 Open-Label, Single-Ascending-Dose Study of EN-374, a Helper-Dependent Adenoviral-Based Gene Therapy, in Participants With X-Linked Chronic Granulomatous Disease
Ensoma
Summary
The goal of this clinical trial is to evaluate the safety and potential efficacy of the EN-374 treatment regimen and identify a dose level for further evaluation in participants with x-linked chronic granulomatous disease. The main questions it aims to answer are: * safety of the EN-374 treatment regimen * effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
Description
Chronic granulomatous disease (CGD) is a rare primary immune deficiency disorder characterized by recurrent bacterial or fungal infections starting in infancy. The x-linked form of CGD (X-CGD) is caused by mutations in the CYBB gene. EN-374 is a helper-dependent adenoviral (HDAd)-based gene therapy in development for the treatment of X-CGD using an in vivo approach, which is administered by IV infusion, to genetically modify hematopoietic stem cells (HSCs) to express a wild-type CYBB gene. The EN-374 treatment regimen includes HSC mobilization, immune prophylaxis, EN-374 administration, and e…
Eligibility
- Age range
- 0+ years
- Sex
- Male
- Healthy volunteers
- No
Inclusion Criteria: * Male * ≥ 18 years of age during dose escalation, then ≥ 3 months of age during dose expansion * Diagnosis of X-CGD with DHR+ cells ≤ 5% and a pathogenic mutation in the CYBB gene * History of at least 1 severe infection requiring medical intervention or chronic inflammatory disorder * Does not have a suitable, available, and willing human leukocyte antigens (HLA)-matched (10/10) related donor * Non-sterile male participants who are or may become sexually active with female partners of childbearing potential are required to use highly effective contraception * Informed co…
Interventions
- GeneticEN-374
Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment
Locations (9)
- University of California, Los AngelesLos Angeles, California
- University of California, San FranciscoSan Francisco, California
- Johns Hopkins All Children's HospitalSt. Petersburg, Florida
- Boston Children's HospitalBoston, Massachusetts
- University of MinnesotaMinneapolis, Minnesota
- Columbia University Irving Medical Center, Morgan Stanley Children's HospitalNew York, New York