Direct Lentiviral Injection Gene Therapy for MLD

Официальное название

Direct Lentiviral TYF-ARSA Injection Gene Therapy for Metachromatic Leukodystrophy (MLD)

Обзор

This is a Phase I/II clinical trial of gene therapy for treating Metachromatic leukodystrophy (MLD) using a safety and efficacy improved self-inactivating lentiviral vector TYF-ARSA to functionally correct the genetic defect. The primary objectives are to evaluate the safety and efficacy of the direct gene transfer clinical protocol.

Подробное описание

Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disease. This disease is an inherited single gene autosomal recessive defect. MLD is caused by a mutation in the ARSA gene encoding arylsulfatase A which leads to a deficiency in sulfatide degradation, resulting in its accumulation in oligodendrocytes, Schwann cells and neurons. A critical level of sulfatide storage can trigger demyelination, the hallmark of MLD, which results in multiple neurological symptoms. MLD has different onset ages including late infancy (1-2 years), adolescence (4 years-before sexual maturity) and adulthood (after sexual maturity). MLD patients are normally rescued by hematopoietic stem cell transplantation (HSCT) from a matched healthy donor. However, HSCT must be performed at a very early stage of the disease thus restricting its therapeutic opportunies in MLD patients. This trial aims to treat MLD using a safety and efficacy improved self-inactivating lentiviral vector (LV) carrying a functional MLD gene to correct the genetic defect by intrathecal (IT) and intravenous (IV) injections to delivery the lentiviral vector carrying a normal ARSA gene to correct the genetic defect. The primary objectives are to evaluate the safety of the improved LV TYF-ARSA and the direct injection gene transfer clinical protocol, the efficacy of degradative metabolite in patients after treatment, vector integration profile, and finally the long-term correction of the related pathological symptoms.

Вмешательства

• Генная терапия Intrathecal and intravenous LV gene therapy
  Direct IT and IV LV gene therapy to deliver high levels of LVs at 1-2×10\^9 transduction units/ml which carry a normal ARSA gene

Первичные конечные точки

• Safety of IT and IV injections of lentiviral TYF-ARSA [Срок оценки: up to 1 year follow up]
• Altered disease progression [Срок оценки: up to 3 year follow up after treatment]
• Altered disease progression [Срок оценки: up to 3 year follow up after treatment]

Критерии участия

Критерии включения

• MLD patient age >= 1 month
• ARSA gene sequence analysis to confirm MLD mutations
• Scoring system for brain MR Imaging confirmed MLD
• Parent / guardian / patient signing informed consent
• Patients and their families have a strong willingness to participate in clinical trials, and are willing to bear all the consequences caused by the failure of the trial, and sign an informed consent form

Критерии исключения

• HIV positive patients
• Patients who are experiencing uncontrolled viral, bacterial or fungal infections, malignant tumors, heart abnormalities, liver dysfunction, or renal insufficiency
• Cannot perform an MRI
• Infection or dermatosis at pre-injection site
• Any condition that may increase the subjects' risk or interfere with the results of the trial. In addition to MLD, there are other neurological disorders.

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

• Lung-Ji Chang — Шэньчжэнь

Идентификаторы

NCT: NCT03725670 · GIMI-IRB-18005

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗