EN-374 gene therapy for X-linked chronic granulomatous disease
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
This will try EN-374, an IV gene therapy, to restore neutrophil function in males with X-linked chronic granulomatous disease.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 15 (estimated) |
| Ages | 3 Months and up |
| Sex | Male |
| Sponsor | Ensoma Industry-sponsored |
| Locations | 9 sites (Los Angeles, California and 8 other locations) |
| Trial ID | NCT06876363 on ClinicalTrials.gov |
What this trial studies
EN-374 is a helper-dependent adenoviral (HDAd) in vivo gene therapy given by IV infusion that aims to genetically modify hematopoietic stem cells to express a working CYBB gene. The treatment regimen includes stem cell mobilization, immune prophylaxis, EN-374 administration, and enrichment of genetically modified HSCs. The trial uses a dose-escalation design in adults followed by age-decreasing pediatric dose-expansion cohorts to identify an appropriate dose. Key outcomes include safety and the production of functional neutrophils with NADPH oxidase activity.
Who should consider this trial
Good fit: Male patients with genetically confirmed X-CGD (pathogenic CYBB mutation) with ≤5% DHR+ neutrophils, a history of at least one severe infection or chronic inflammatory disorder, and no suitable HLA-matched related donor are the intended candidates, with adults entering dose escalation and children enrolled later in defined age cohorts.
Not a fit: Patients with active bloodstream infections, prior hematopoietic stem cell transplant or granulocyte transfusions, chronic viral infections like HIV or hepatitis B/C, significant medical or social issues that increase risk or interfere with care, and females (not eligible) are unlikely to receive benefit from this protocol.
Why it matters
Potential benefit: If successful, EN-374 could restore NADPH oxidase activity in patients' neutrophils and reduce the frequency and severity of infections and inflammatory complications.
How similar studies have performed: Ex vivo HSC gene therapies using lentiviral vectors have shown benefit in CGD, but the in vivo HDAd-based approach used by EN-374 is relatively novel and unproven in humans.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Los Angeles, California and 8 other locations
- University of California, Los Angeles — Los Angeles, California, United States (Recruiting)
- University of California, San Francisco — San Francisco, California, United States (Recruiting)
- Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States (Recruiting)
- Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
- University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
- Columbia University Irving Medical Center, Morgan Stanley Children's Hospital — New York, New York, United States (Recruiting)
- Duke University — Durham, North Carolina, United States (Recruiting)
- University of Utah, Primary Children's Hospital — Salt Lake City, Utah, United States (Recruiting)
- University College London Hospital — London, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Andrew Dietz, MD, MSCR
- Email: ddietz@ensoma.com
- Phone: 617-766-3917
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.