LENTICOL-F

  • Research type

    Research Study

  • Full title

    Phase 1 study of lentiviral-mediated COL7A1 gene-modified autologous fibroblasts in adults with recessive dystrophic epidermolysis bullosa.

  • IRAS ID

    164308

  • Contact name

    John McGrath

  • Contact email

    john.mcgrath@kcl.ac.uk

  • Sponsor organisation

    King's College London (King's Health Partners)

  • Eudract number

    2014-004884-19

  • Duration of Study in the UK

    3 years, 7 months, 1 days

  • Research summary

    This study aims to assess whether it is safe to inject COL7A1 gene-modified skin cells (fibroblasts) into the intact skin of adults with recessive dystrophic epidermolysis bullosa (RDEB) – a rare severe form of inherited blistering skin disease due to lack of type VII collagen (C7) protein in the skin (C7 glues the major skin layers together), caused by damage in COL7A1 gene. The idea is that genetically modified fibroblasts could potentially restore C7 in these individuals with RDEB, leading to fewer blisters and stronger skin. Fibroblasts will be extracted and grown from each participant's own skin sample in the laboratory: Cellular Therapies at Great Ormond Street Hospital (GOSH) under strict Good Manufacturing Practice conditions. A form of disabled virus (lentivirus) will be used to insert the corrected copy of COL7A1 gene into these fibroblasts (gene-modified fibroblasts). Once sufficient cell numbers are grown, we will administer 3 injections of these gene-modified fibroblasts back into the participant's own intact skin (as opposed to blistering areas) in order to effectively assess their safety. We aim to recruit 5-10 adults with RDEB from Guy’s and St Thomas’ NHS Trust (GSTT) as per the trial eligibility criteria.

    History, examination and vital signs will be performed at each visit for 36 months and clinical photographs of the injection sites taken up to 20 months after the injections. There will be a total of 10 blood tests over 36months and 14 skin biopsies (1x6mm and 13x4mm punch biopsies) over 12 months. We will examine from the biopsies what happens to C7 production in the skin. If this phase 1 study demonstrates the safety of gene-modified fibroblasts then a phase 2 powered control study with a larger sample size can be carried out to evaluate efficacy in the future.

  • REC name

    London - West London & GTAC Research Ethics Committee

  • REC reference

    15/LO/0665

  • Date of REC Opinion

    28 May 2015

  • REC opinion

    Favourable Opinion