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 - EBGraft

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2016-002790-35-FR
• Lead Sponsor: INSERM

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-17
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 3

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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. ;<br> Secondary Objective: The secondary objectives are:<br> 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;<br> 2) To evaluate the immune response against the recombinant C7 at M1, M3, M6 and M12 after grafting;<br> ;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.