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

August 20, 2026 updated by: Ensoma

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, NW1 2PG
        • University College London Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
    • Florida
      • St. Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • University of Minnesota
    • New York
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center, Morgan Stanley Children's Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • University of Utah, Primary Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male
  • ≥ 18 years of age during dose escalation, then ≥ 3 months of age during dose expansion
  • Diagnosis of X-CGD with 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EN-374
Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment
Genetic: EN-374
Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of EN-374
Time Frame: From start of mobilization until Month 12

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
Time Frame: From infusion of EN-374 until Month 12
  • Change from baseline in the percentage of dihydrorhodamine (DHR)+ neutrophils
  • Change from baseline in the percentage of participants with ≥ 10%, 20%, 30%, 40%, or 50% DHR+ neutrophils
From infusion of EN-374 until Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ensoma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2025

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

March 10, 2025

First Submitted That Met QC Criteria

March 10, 2025

First Posted (Actual)

March 14, 2025

Study Record Updates

Last Update Posted (Actual)

August 21, 2026

Last Update Submitted That Met QC Criteria

August 20, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EN-374-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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