Clinical Trial: Safety Study of Gene-modified Autologous Fibroblasts in Recessive Dystrophic Epidermolysis Bullosa
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.
Brief Summary: 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.
Detailed Summary:
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 36 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.
Sponsor: King's College London
Current Primary Outcome: Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period. [ Time Frame: 12 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
- Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
- Vector copy number, measured by q-PCR, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
- Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence [ Time Frame: Week 2, Month 1, Month 3, Month 6 and Month 12 ]
- T-cell responses to full length type VII collagen measured by ELISPOT [ Time Frame: Week 2, Month 1, Month 3, Month 6 and Month 12 ]
Original Secondary Outcome: Same as current
Information By: King's College London
Dates:
Date Received: May 21, 2015
Date Started: September 2015
Date Completion: November 2019
Last Updated: May 3, 2016
Last Verified: May 2016