Overview
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
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
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