Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period.
研究概览
简要总结
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.
详细描述
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.
This is an open-label single-centre phase I study with primary objective to evaluate the adverse and serious adverse events over 12 months' follow-up period. Secondary objectives include (1) analysis of type VII collagen (C7) expression and morphology of anchoring fibrils in the injected areas of the skin; (2) analysis of immune response to newly expressed C7.
Each study participant will receive three intradermal injections of COL7A1 gene-modified autologous fibroblasts on Day 0 only. Each subject will undergo an initial screening including a physical examination and assessment of disease severity. Blood analyses and skin biopsies will be performed at various time points as per the monitoring schedule over 12 months.
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
- 17 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical and genetic diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations.
- •A reduced number or morphologically abnormal anchoring fibrils confirmed by TEM.
- •At least 5x8cm of intact skin on the trunk and/or extremities that is suitable for cell injections.
- •Able to undergo local anaesthesia.
- •Subjects aged ≥ 17 years and able to give informed consent prior to the first study intervention.
排除标准
- •Subjects who received other investigational medicinal products within 6 months prior to enrolment into this study.
- •Past medical history of biopsy proven skin malignancy.
- •Subjects who have received immunotherapy including oral corticosteroids (Prednisolone >1mg/kg) for more than one week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study.
- •Known allergy to any of the constituents of the investigational medicinal product (IMP).
- •Subjects with BOTH:
- •positive serum antibodies to C7 confirmed by ELISA and
- •positive IIF with binding to the base of salt split skin.
- •Subjects who are pregnant or of child-bearing potential who are neither abstinent nor practising an acceptable means of contraception when this is in line with the usual and preferred lifestyle of the subject, as determined by the Investigator, for 12 months after the cell injections.
- •Subjects with positive results for HIV, Hepatitis B, Hepatitis C, HTLV or Syphilis.
研究组 & 干预措施
Gene-modified autologous fibroblasts
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
干预措施: Gene-modified autologous fibroblasts (Drug)
结局指标
主要结局
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period.
时间窗: 12 months
次要结局
- Vector copy number, measured by q-PCR, in the treated and untreated skin(Week 2, Month 3 and Month 12)
- T-cell responses to full length type VII collagen measured by ELISPOT(Week 2, Month 1, Month 3, Month 6 and Month 12)
- Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence(Week 2, Month 1, Month 3, Month 6 and Month 12)
- Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin(Week 2, Month 3 and Month 12)
- Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin(Week 2, Month 3 and Month 12)