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

NCT06876363 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: EN-374-101
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 9

Brief 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

Conditions

X-Linked Chronic Granulomatous Disease

Keywords

CGD; X-CGD; Chronic Granulomatous Disease; X-Linked Chronic Granulomatous Disease; Granulomatous Disease, Chronic; Genetic Therapy; Gene Therapy; in vivo Gene Therapy; Gene Addition Therapy; in vivo Gene Addition Therapy; Hematopoietic Stem Cell Gene Therapy; in vivo Hematopoietic Stem Cell Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Safety of EN-374

  Incidence rate across all age groups of: * treatment-emergent adverse events (TEAEs) * treatment-related TEAEs (TRAEs) * serious adverse events (SAEs)

  From start of mobilization until Month 12

Secondary Outcomes (1)

• Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity

  From infusion of EN-374 until Month 12

Study Arms (1)

EN-374

EXPERIMENTAL

Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment

Genetic: EN-374

Interventions

EN-374 GENETIC

Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment

EN-374

Eligibility Criteria

• Age: 3 Months+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 consent, with informed assent from capable participants
• Adequate organ function

You may not qualify if:

• Active bacteremia or fungemia
• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• History or clinical evidence of any medical or social issues likely to put the participant at additional risk or to interfere with study conduct
• History of HSCT or granulocyte transfusions
• Known hypersensitivity to elements in the treatment regimen
• Undergone investigational gene therapy
• Treated with another investigational drug product within 30 days before screening
• Unable to comply with the visits and requirements of the protocol as determined by the Investigator

Sponsors & Collaborators

• Ensoma: lead

Study Sites (9)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94158, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55454, United States

RECRUITING

Columbia University Irving Medical Center, Morgan Stanley Children's Hospital

New York, New York, 10032, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

University of Utah, Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

University College London Hospital

London, NW1 2PG, United Kingdom

RECRUITING

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Andrew Dietz, MD, MSCR

CONTACT

617-766-3917; ddietz@ensoma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 14, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

GB (1); US (8)