The trial aims to treat the recessive dystrophic epidermolysis bullosa (RDEB) by grafting one to three subjects with RDEB with autologous COL7A1-modified skin equivalents, using SIN-RV encoding COL7A1 cDNA. MedDRA version: 20.0 Level: LLT Classification code 10074980 Term: Epidermolysis bullosa aquisita System Organ Class: 100000004858
Conditions
Interventions
Product Name: SIN RV-mediated COL7A1 corrected autologous skin equivalent
Pharmaceutical Form:
Sponsors
INSERM
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. = 18 year-old 2. Clinical and molecular diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations 3. Significantly reduced staining of C7 on skin biopsy, measured by immunofluorescence microscopy (IF) 4. A reduced number of or morphologically abnormal anchoring fibrils confirmed by TEM 5. Presence of non-collagenous-1 domain (NC-1) of C7 on skin biopsy, measured by immunofluorescence microscopy (IF) and/or Western blot analysis 6. Presence of =100cm2 of blistered and/or erosive skin areas including chronic wounds suitable for skin grafting 7. Ability to undergo anaesthesia for grafting procedures 8. Subjects aged = 18years, willing and able to give informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Recipients of other investigational medicinal products within 6 months prior to enrolment into this study 2. Past medical history of biopsy proven skin malignancy 3. Immunotherapy including oral corticosteroids (Prednisolone >1mg/kg) for more than one week (intranasal and topical preparations are permitted) or chemotherapy within 60 days of enrolment into this study 4. Known allergy to any of the constituents of the investigational medicinal product (IMP) including Penicillin 5. Subjects with BOTH: • positive serum antibodies to C7 confirmed by ELISA and • positive IIF with binding to the base of salt split skin and/or • positive Western blot 6. Positive results for HIV, Hepatitis BsAg, Hepatitis BcAb, Hepatitis C IgG, HTLV1&2 or Syphilis serology 7. Clinically significant medical, psychological or laboratory abnormalities limiting the ability of the subject to travel to the trial site(s) and to undergo grafting and follow-up procedures, as determined by the Investigator 8. Absence of adequate social support 9. Subjects who are pregnant, breast-feeding or of child-bearing potential who are neither abstinent nor practicing an acceptable means of contraception when this is in line with the usual and preferred lifestyle of the subject, as determined by the Investigator, for the duration of the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this phase I/II clinical trial is to evaluate the safety of grafting SIN RV-mediated COL7A1 gene-modified autologous SE in adults with RDEB. ;Secondary Objective: The secondary objectives are: 1) To assess the efficacy of SIN RV-mediated COL7A1 gene-modified autologous SE in adults with RDEB at W2, M1, M3, M6 and M12 after grafting; 2) To evaluate the immune response against the recombinant C7 at M1, M3, M6 and M12 after grafting; ;Primary end point(s): Primary Endpoints: Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over a 12 months follow-up period.;Timepoint(s) of evaluation of this end point: At each visit over a 12 months follow-up period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Molecular endpoints 1) Skin biopsy analysis of grafted skin at M1, M3, M6 and M12 compared to baseline for: a) C7 protein expression by immunofluorescence microscopy (IF) b) Morphology of anchoring fibrils (AFs) at the dermal-epidermal junction (DEJ) by transmission electron microscopy (TEM) 2) Serum analysis at M1, M6 and M12 compared to baseline for: a) Detection of anti-C7 antibodies by enzyme-linked immunosorbent assay (ELISA) (against the entire C7 molecule) indirect immunofluorescence (IIF) and/or Western blot (WB) b) Detection of T-cell responses to the full length C7 by enzyme-linked immunosorbent spot (ELISPOT) assay Clinical endpoints Clinical assessment at M1, M3, M6 and M12 compared to baseline for: a) The scar quality measured by the Vancouver Scar Scale (VSS) b) Changes in blister numbers over the grafted skin c) Changes in the clinical appearance of grafted skin through clinical photographs at each visit d) Changes in pruritus measured by the Leuven Itch Scale (LIS) e) Changes in Quality of Life Score measured by the QOLEB ;Timepoint(s) of evaluation of this end point: Molecular endpoints 1) Skin biopsy analysis of grafted skin at M1, M3, M6 and M12 2) Serum analysis at M1, M6 and M12 Clinical endpoints Clinical assessment at M1, M3, M6 and M12 | — |
Countries
France
Contacts
Public ContactSonia GUEGUEN
INSERM
Outcome results
None listed