Clinical trial NCT06876363: Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Ensoma
Sponsor class: INDUSTRY
First posted: 2025-03-14
Enrollment: 15
Sex: MALE
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety of EN-374
timeFrame: From start of mobilization until Month 12
Secondary outcomes:
measure: Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity
timeFrame: From infusion of EN-374 until Month 12
Other outcomes:
Locations:
Study officials:
References: