Gene Therapy for SCID-X1 Using a Self-inactivating (SIN) Gammaretroviral Vector
试验速览
- 阶段
- 不适用
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Immunological reconstitution
研究概览
简要总结
X-linked severe combined immunodeficiency (SCID-X1) is an inherited disorder that results in failure of development of the immune system in boys. This trial aims to treat SCID-X1 patients using gene therapy to replace the defective gene.
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
- — 至 16 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •No HLA identical (A,B,C,DR,DQ) family donor and no HLA identical unrelated donor available within 3 months of diagnosis or patients whose underlying clinical problems and prognosis would be significantly compromised by chemotherapy conditioning (including persisting pneumonitis, protracted diarrhoea requiring parental nutrition, ongoing visceral viral infection (herpes viruses, HSV,VZV,CMV, EBV or adenovirus), systemic BCG infection, virus-induced lymphoproliferation.
- •Diagnosis of classical SCID-X1 based on immunophenotype (absent, or reduced numbers of non-functional T lymphocytes) and confirmed by DNA sequencing
- •Parental/guardian voluntary consent
- •Boys between the ages of 0 and 16
排除标准
- 未提供
研究组 & 干预措施
Single infusion of autologous CD34+ cells
干预措施: Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) gammaretroviral vector pSRS11.EFS.IL2RG.pre (Genetic)
结局指标
主要结局
Immunological reconstitution
时间窗: 1-18 months post-infusion,then annually
* Immunophenotyping: detection of naïve CD3+ T-cell numbers, CD4, CD8, TCRαβ, TCRγδ, CD16+CD56+ NK \& gamma chain expression. TRECs may be enumerated as surrogate marker for new thymic emigrants post-gene therapy * Lymphocyte proliferation assays to test function of T cells * Representation of TCR families by flow cytometry (Vβ phenotyping), \& CDR3 PCR spectratyping (Vβ spectratyping) to monitor physiological \& potentially pathological clonal expansions * Restoration of antibody production (IgA, IgM, IgG) \& serological responses to vaccinations \& natural infections.
次要结局
- Incidence of adverse reactions(from consent until 5 years post-infusion of gene-modified cells)
- Molecular characterisation of gene transfer(until 5 years post-infusion of gene-modified cells)
- Normalisation of nutritional status, growth, and development(until 5 years post-infusion of gene-modified cells)