A Phase I/II, Non Randomized, Multicenter, Open-label Study of Autologous CD34+ Cells Transduced With the G1XCGD Lentiviral Vector in Patients With X-linked Chronic Granulomatous Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Genethon
- 入组人数
- 3
- 试验地点
- 3
- 主要终点
- Safety of the procedure as measured by the incidence of adverse events
研究概览
简要总结
X-linked chronic granulomatous disease (X-CGD) is a rare genetic disorder, which affects boys. It is caused by an error in a gene that makes part of the immune system. The basic defect lies in specialised white blood cells called phagocytic cells (or phagocytes), which are responsible for protection against infection by destroying invading bacteria and fungi. They do this by pouring large amounts of substances similar to bleach onto these organisms. In CGD, there is a defect in the system that makes the bleach, called the NADPH-oxidase. In X-CGD (which accounts for two thirds of patients), the defect lies in a gene which makes up a critical part of the NADPH-oxidase (known as gp91-phox), and the cells cannot make bleach-like substances. Therefore they kill bacteria and fungi poorly, and the patients suffer from severe and recurrent infections. This also results in inflammation which can damage parts of the body such as the lung and gut.
In many cases, patients can be adequately protected from infection by constant intake of antibiotics. However, in others, severe life-threatening infections break through. In some cases, inflammation in the bowel or urinary systems results in blockages which cannot be treated with antibiotics, and which may require the use of other drugs such as steroids. Development of curative treatments for CGD is therefore of great importance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male X-CGD patients
- •Molecular diagnosis confirmed by DNA sequencing
- •At least one prior ongoing or resistant severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy
- •No HLA-matched donor available after 3 months search unless the risk of waiting for a potential match or for performing an allogeneic transplant is considered unacceptable by the investigator
排除标准
- •Contraindication for leukapheresis
- •Contraindication for administration of conditioning medication
- •Administration of gammainterferon within 30 days before the infusion of transduced autologous CD34+ cells
研究组 & 干预措施
Open label
X vivo gene therapy
干预措施: X vivo gene therapy (Genetic)
结局指标
主要结局
Safety of the procedure as measured by the incidence of adverse events
时间窗: 24 months
Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test
时间窗: 12 months
次要结局
- Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time(24 months)
- Immunological reconstitution(24 months)
- Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion(24 months)