X-Linked Chronic Granulomatous Disease
Conditions
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
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.
Interventions
GENETICEN-374
Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment
Sponsors
Ensoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
3 Months to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of EN-374 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity | 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 |
Countries
United Kingdom, United States
Outcome results
None listed