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

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Генная терапия EN-374
  Single dose of EN-374 administered by intravenous infusion after mobilization and followed by enrichment

Первичные конечные точки

• Safety of EN-374 [Срок оценки: From start of mobilization until Month 12]

Вторичные конечные точки (1)

• Effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity [Срок оценки: From infusion of EN-374 until Month 12]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• University of California, Los Angeles — Los Angeles
• University of California, San Francisco — San Francisco
• Johns Hopkins All Children's Hospital — St. Petersburg
• Boston Children's Hospital — Boston
• University of Minnesota — Minneapolis
• Columbia University Irving Medical Center, Morgan Stanley Children's Hospital — New York
• Duke University — Durham
• University of Utah, Primary Children's Hospital — Salt Lake City

Великобритания · 1 центр

• University College London Hospital — London

Идентификаторы

NCT: NCT06876363 · EN-374-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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