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

NCT ID: NCT06876363

Last Updated: 2025-11-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-05

Study Completion Date

2027-12-31

Brief Summary

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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

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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

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X-Linked Chronic Granulomatous Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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EN-374

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

Group Type EXPERIMENTAL

EN-374

Intervention Type GENETIC

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

Interventions

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EN-374

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

Intervention Type GENETIC

Eligibility Criteria

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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 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
Minimum Eligible Age

3 Months

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Ensoma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

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

New York, New York, United States

Site Status RECRUITING

Duke University

Durham, North Carolina, United States

Site Status RECRUITING

University of Utah, Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Andrew Dietz, MD, MSCR

Role: CONTACT

617-766-3917

Facility Contacts

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Alli Travis, BSN, RN, BMTCN

Role: primary

612-625-6150

Brianna Mayo, PNP, RN

Role: primary

212-305-2372

Linda Brown

Role: primary

919-613-1482

Morgan Badgley, BS, CCRC

Role: primary

801-662-4812

Chelsie Tucker, BS, CRC

Role: backup

801-662-4813

Other Identifiers

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EN-374-101

Identifier Type: -

Identifier Source: org_study_id

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