Open-label, Pivotal Clinical Trial to Confirm Efficacy and Safety of Autologous Grafts Containing Stem Cells Genetically Modified for Epidermis Restoration in Patients With Junctional Epidermolysis Bullosa

Prospective, multicenter and multinational, open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified transduced with a LAMB3-gamma retroviral vector. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 5) for restoration of the epidermis in patients with generalized intermediate LAMB3-dependent Junctional Epidermolysis Bullosa.

This trial aims to prove the efficacy and safety of RV-LAMB3-transduced epidermal stem cells and lead to a permanent therapy for the skin lesions affecting JEB patients. Patients are screened according to the Study Inclusion and Exclusion criteria and if found eligible, participants are candidate for the treatment. After confirmation of eligibility, patients will undergo to biopsy for the collection of the autologous epidermal cells used to produce the tissue for the treatment. If all criteria are met, the transplantation of the new cultured transgenic epidermis will be planned according to the procedures and the need of the patient. The study treatment consists of a surgical intervention for new restored stem cells implantation. The surgery is carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy is processed in a laboratory of a regenerative medicine manufacturing site where the tissue is corrected, expanded and prepared as final sheets to be implanted. Afterward, the patient undergoes to the second intervention when the grafts containing genetically corrected cultured keratinocytes (Hologene-5) are implanted into the selected area under local or general anaesthesia. The treated area is then immobilized for some days after this surgery. Antibiotics and anti-inflammatory drugs may be administered (if necessary) to prevent infections and to minimise swelling. The follow-up after implantation is 12 months. The treatment can be repeated. The end of the trial is defined as the last visit of the last patient after the last treatment.