Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
This is a Phase I/II clinical trial of gene therapy for treating Chronic Granulomatous Disease using a high-safety, high-efficiency, self-inactivating lentiviral vector TYF to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the TYF-CGD gene transfer clinical protocol.
详细描述
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
Chronic granulomatous disease (CGD) is a rare disorder caused by inherited defects in the NADPH oxidase multienzyme complex. It is associated with severe and life-threatening bacterial and fungal infections. Approximately two-thirds of all CGD cases result from mutations within the X-linked gp91phox gene (CYBB), followed by the autosomal recessive forms of CGD, with defects in the gene coding for p47phox (NCF1) accounting for 10-30% of all CGD cases.
The primary objectives are to evaluate the safety of the advanced self-inactivating lentiviral vector TYF-CYBB and TYF-NCF1, the ex-vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment, assessment of vector integration sites, and finally the long-term correction of immune dysfunctions.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CGD patients >= 0 years of age
- •Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
- •Karnofsky-Index > =70%
- •At least one prior, ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite drug intervention
- •Written informed consent for adult patient, and assent for pediatric subjects seven years or older
排除标准
- •Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
- •Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test
研究组 & 干预措施
Lentiviral TYF-CGD-modified autologous stem cells
Autologous hematopoietic stem cells transduced with lentiviral TYF vector carrying the functional gene
干预措施: Infusion of lentiviral TYF-CGD-modified autologous stem cells (Genetic)
结局指标
主要结局
Overall survival
时间窗: 15 year follow up
Patient will be monitored for overall health condition, including immune cell assessments, blood biochemistry and metabolitic activities, metabolic detoxification.
Gene marking in bone marrow cells
时间窗: 15 year follow up
Gene-modified cells in the bone marrow will be measured by vector-specific quantitative PCR of colony-forming cells. Patient overall survival will be followed up for 15 years.
次要结局
- Recovery of immune function(1 year follow up)
- Change in infection frequency(1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests)