Evaluating the Safety and Efficacy of Decitabine in the Treatment of XMEN Patients

Официальное название

Single-arm Clinical Study Evaluating the Safety and Efficacy of Decitabine in the Treatment of X-linked MAGT1 Deficiency With Increased Susceptibility to EBV Infection and N-linked Glycosylation Defect (XMEN) Patients

Обзор

This is a single-arm, open-label, single-center, exploratory clinical trial evaluating the safety and efficacy of decitabine in male patients aged 1 month to 18 years with X-linked magnesium transporter 1 (MAGT1) deficiency. Eligible patients have a confirmed MAGT1 gene mutation leading to XMEN disease ( X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus (EBV) infection and N-linked glycosylation defect). The study will assess changes in liver function, immune function, and NKG2D expression, as well as adverse events, over four treatment cycles and the follow-up period.

Подробное описание

XMEN disease is a rare X-linked primary immunodeficiency caused by loss-of-function mutations in MAGT1, leading to chronic Epstein-Barr virus (EBV) infection, liver dysfunction, and reduced NKG2D expression on lymphocytes. TUSC3 shares functional redundancy with MAGT1 but is epigenetically silenced in immune and liver tissues. Decitabine, a DNA methyltransferase inhibitor, can reactivate TUSC3 expression.

This single-arm, open-label, single-center study will enroll six male participants aged 1 month to 18 years with genetically confirmed MAGT1 mutation and a clinically diagnosis of XMEN disease. Eligible participants will receive decitabine intravenously at 20 mg/m² once daily for five consecutive days every four weeks, for a total of four cycles. Safety and efficacy will be evaluated by monitoring NKG2D expression, liver enzymes levels, EBV viral load, lymphocyte function, TUSC3 expression, and adverse events. Participants will be followed for 180 days after the last dose.

Вмешательства

• Препарат Decitabine
  Decitabine 20 mg/m² intravenous infusion once daily for 5 consecutive days every 4 weeks, for a total of 4 cycles.

Первичные конечные точки

• Improvement magnitude of serum liver enzyme levels [Срок оценки: up to 6 months after the last dose]
• Changes in NKG2D expression levels [Срок оценки: up to 6 months after the last dose]
• Cumulative incidence of grade ≥3 myelosuppression [Срок оценки: up to 6-month follow-up period after the last dose]

Вторичные конечные точки (4)

• Changes in TUSC3 expression in peripheral blood lymphocytes [Срок оценки: up to 6-month after the last dose]
• Increase in cytotoxic activity of NK cells/T cells [Срок оценки: up to 6 months after the last dose]
• Cumulative incidence of coagulation dysfunction [Срок оценки: up to 6 months after the last dose]
• Overall incidence rate of adverse events and severity grading [Срок оценки: up to 6 months after the last dose]

Критерии участия

Критерии включения

• Male participants aged 1 month to 18 years old.
• Confirmed MAGT1 gene mutation by genetic testing.
• Clinical manifestations consistent with XMEN disease, including liver dysfunction and/or EBV infection.
• Reduced lymphocyte NKG2D expression.
• Vital signs within normal range at screening.
• Expected survival ≥ 6 months.
• Able to comply with study procedures.
• Guardian and participant provide written informed consent.

Критерии исключения

• Hypersensitivity to decitabine or any excipient.
• Hematopoietic stem cell transplantation within 1 year before enrollment.
• Severe concurrent organ dysfunction or systemic disease.
• Positive HBsAg, anti-HCV, syphilis, or HIV test.
• Neurological or psychiatric disorders that impair compliance.
• Participation in another clinical trial within 3 months.
• Other conditions judged inappropriate 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

Китай · 1 центр

• Children's Hospital of Fudan University — Шанхай

Публикации

• Ding H, Li Y, Fang M, Chen J, Liu L, Lu Z, Hou J, Luo M. Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease. J Allergy Clin Immunol. 2023 Jun;151(6):1622-1633.e10. doi: 10.1016/j.jaci.2023.04.003. Epub 2023 Apr 21. PMID 37086924

Идентификаторы

NCT: NCT07555405 · IIT2026008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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