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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
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
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
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