This study is in progress, not accepting new patients

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

a study on Chronic Granulomatous Disease

Summary

Eligibility
for males ages 3 months and up (full criteria)
Location
at UCLA UCSF
Dates
study started
study ends around
Principal Investigator
by Morna Dorsey (ucsf)
Headshot of Morna Dorsey
Morna Dorsey

Description

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

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

Details

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.

Keywords

X-Linked Chronic Granulomatous Disease, CGD, X-CGD, 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

Eligibility

You can join if…

Open to males ages 3 months and up

  • 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

You CAN'T join 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

Locations

  • University of California, Los Angeles
    Los Angeles California 90095 United States
  • University of California, San Francisco
    San Francisco California 94158 United States

Lead Scientist at University of California Health

  • Morna Dorsey (ucsf)
    My research interests lie in three main focus areas: 1. Optimizing diagnosis and care of patients with primary immunodeficiency 2. Investigating the psychosocial impact of primary immunodeficiency on patients and families 3. Establishing treatment for patients with food allergy and eosinophilic disorders

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Ensoma
ID
NCT06876363
Phase
Phase 1/2 Chronic Granulomatous Disease Research Study
Study Type
Interventional
Participants
Expecting 15 study participants
Last Updated