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
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
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 enrichment of genetically modified HSCs.
Adult participants with X-CGD will be enrolled into the dose-escalation part of the study. Following completion of the adult cohorts, then pediatric participants will be enrolled into the dose-expansion part of the study in decreasing age cohorts from ≥ 12 and < 18 years of age, to ≥ 2 and < 12 years of age, and finally to ≥ 3 months and < 2 years of age.
