NCT06876363

Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Ensoma · Industry
• Sex: Male
• Age: 3 Months
• Healthy volunteers: Not accepted

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

Detailed 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 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.

Conditions

• X-Linked Chronic Granulomatous Disease

Interventions

Type	Name	Description
GENETIC	EN-374	Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment

Timeline

• Start date: 2025-08-05
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2025-03-14
• Last updated: 2026-03-31

Locations

9 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study