No patient ongoing (none completed the study). Changes to the viral vector ongoing.

Prospective open-label, uncontrolled clinical study to assess the safety and efficacy of autologous cultured epidermal grafts containing epidermal stem cells genetically modified with the aid of a gamma-retroviral vector carrying COL17A1 complementary DNA (cDNA) for restoration of the epidermis in patients with junctional epidermolysis bullosa. The purpose of this study is to demonstrate the safety and efficacy after one or more treatments with genetically corrected cultured epidermal autograft (Hologene 17) in patients suffering of junctional epidermolysis bullosa (JEB) with COL17A1 mutation.

This is a prospective, open label, uncontrolled clinical trial, phase I/II. Patients will be screened according to the Study Inclusion and Exclusion criteria and will be candidate for the treatment if all inclusion and none of the exclusion criteria are met.

After confirmation of eligibility, patients will undergo biopsy for the collection of the autologous epidermal cells to be used to produce the tissue for the treatment. In case 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 will be carried out in 2 stages, the first aims at taking biopsy to isolate epidermal cells including stem cells. The biopsy will be processed in a laboratory of a regenerative medicine manufacturing site where they will be corrected, expanded and prepared as final sheets to be implanted. Therefore, the patient can have his second intervention. In this second surgery, genetically corrected cultured epidermal autograft (Hologene 17) will be implanted into the selected area. The specialist surgeon will either use a local or general anaesthetic for the transplant operation. The treated area will be immobilized for some days after this operation. Antibiotics and anti-inflammatory drugs will be administered (if necessary) to prevent infections and to minimise swelling.

Three months after the transplantation, primary endpoint will be evaluated by the Investigator. The study completion will be reached when 1 year (secondary endpoint) of follow-up after the last transplant in the last patient will be accomplished.

The end of the trial is defined as the last visit of the last patient after the last treatment if any.

Inclusion Criteria:

1. Signed and dated informed consent prior to any study-related procedures;
2. Male and female patients between 6 years old to 54 years old;
3. JEB molecular characterization by mutation analysis;
4. NC16A antibody immunofluorescence or positive staining in Western Blot analysis with polyclonal antibody produced against a synthetic peptide corresponding to amino acids 131-145 of human COL17A1;
5. Presence of chronic (persistent or recurrent for more than 3 months) large wounds (>10 cm2) and/or persistent or recurrent erosions;
6. A cooperative attitude to follow up the study procedures (Caregivers in case of minors).

Exclusion Criteria:

1. Known or suspected intolerances against anaesthesia;

2. Bad general condition (ECOG index >1);

3. Unresectable metastasizing Squamous Cell Carcinomas (SCCs);

4. Antibodies to type XVII collagen associated antigens demonstrated on indirect immunofluorescence;

5. Clinical and/or laboratory signs of acute systemic infections at the time of screening. Patient can be re-screened after appropriate treatment;

6. Severe systemic diseases (i.e. uncompensated diabetes mellitus);

7. Female subjects: pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use one or more reliable methods of contraception with a Pearl index ≤1. Reliable contraception should be maintained throughout the study.

8. Allergy, sensitivity or intolerance to drugs, excipients or other material (as per Investigator's brochure):

   • Transport medium (Dulbecco's Modified Eagles Medium supplemented with L-glutamine)
   • Fibrin support
   • Povidone iodine

9. Contraindications to the local or systemic antibiotics and/ or corticosteroids foreseen by the protocol;

10. Contraindications to undergo extensive surgical procedures;

11. Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation based upon investigator's judgment or other concomitant medical conditions affecting grafting procedure;

12. Patients (or parents in case of paediatric subject) unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study procedures and treatments;

13. Participation in another clinical trial where investigational drug was received less than 6 months prior to screening Visit.