Phase I/II ex vivo gene therapy clinical trial for RDEB using autologous skin equivalent grafts genetically corrected with a COL7A1-encoding SIN retroviral vector
Lay summary
This clinical trial aims to treat chronic wounds of three adult patients affected with recessive dystrophic epidermolysis bullosa (RDEB) using skin equivalents made of their own epidermal and dermal cells genetically corrected with a secured viral vector expressing a normal copy of the Collagen VII gene.
RDEB is a severe genetic skin disease caused by loss-of-function mutations (faults) in the Collagen VII gene. Patients with RDEB suffer from skin detachment upon minor trauma. A total surface of up to 300 cm2 will be grafted per patient. These patients have been chosen because they express very low amounts of Collagen VII and have severe chronic wounds that impair their quality of life.
The first goal of the trial is to show that the treatment is safe. The second aim is to evaluate the efficacy of the procedure to prevent skin blistering in the treated areas and to evaluate the immune tolerance to normal Collagen VII at different times after grafting (at months one, three, six and 12) and every four months for the second year.
Scientific Summary
This is a phase I/II open-label non-randomized single-centre clinical trial which aims at grafting chronic wounds of three adult patients with intermediate RDEB using autologous skin equivalents genetically corrected with a secured Self Inactivating (SIN) COL7A1 retroviral vector.
The three patients produce very low levels of Collagen VII. A total surface of up to 300 cm2 of gene-corrected reconstructed skin will be grafted per patient. The primary objective is to evaluate the safety of the approach. The secondary objectives are to assess efficacy using molecular and clinical endpoints and to evaluate the immune response against Collagen VII at month one, month three, month six and month 12, and every 4 months for the second year.