Ex Vivo Gene Therapy Clinical Trial for RDEB Using Genetically Corrected Autologous Skin Equivalent Grafts

NCT04186650 | Active Not Recruiting Phase 1

• 2 other identifiers: C12-482016-002790-35
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II clinical trial aims to treat 3 adult subjects with Recessive Dystrophic Epidermolysis Bullosa, expressing residual C7 levels, by genetically corrected autologous skin equivalent grafts on selected areas (up to 300 cm2).

Conditions

Epidermolysis Bullosa Dystrophica, Recessive

Keywords

Genetic Therapy; Autologous Skin Graft; SIN retroviral vector; Type VII collagen; COL7A1

Outcome Measures

Primary Outcomes (1)

• Safety of grafting SIN RV-mediated COL7A1 gene-modified autologous skin equivalent: Adverse Events (AE), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs)

  The primary objective is to evaluate the safety of autologous autologous skin equivalent grafts genetically corrected with a SIN COL7A1 retroviral vector (RV) in adults with RDEB Primary Endpoints: Record of Adverse Events (AE), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs).

  Month 12 post grafting.

Secondary Outcomes (13)

• Change in C7 protein expression

  Month 1, Month 3, Month 6, Month 12 post grafting.

• Change in anchoring fibrils number

  Month 1, Month 3, Month 6, Month 12 post grafting.

• Change in scar quality: Vancouver Scar Scale (VSS)

  Month 1, Month 2, Month 3, Month 6, Month 12 post grafting.

• Changes in blister number over the grafted skin

  Month 1, Month 2, Month 3, Month 6, Month 12 post grafting.

• Changes in clinical appearance of grafted skin

  Month 1, Month 2, Month 3, Month 6, Month 12 post grafting.

Study Arms (1)

Autologous genetically modified tissue-engineered skin graft

EXPERIMENTAL

Graft of SIN RV-mediated COL7A1 gene-modified autologous skin equivalent

Biological: COL7A1-SIN retroviral vector engineered autologous tissue-engineered skin

Interventions

COL7A1-SIN retroviral vector engineered autologous tissue-engineered skin BIOLOGICAL

Graft of SIN RV-mediated COL7A1 gene-modified autologous skin equivalent

Autologous genetically modified tissue-engineered skin graft

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical and molecular diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations
• Reduced staining of C7 on skin biopsy, measured by immunofluorescence microscopy (IF)
• A reduced number of/or morphologically abnormal anchoring fibrils confirmed by TEM
• Detection of non-collagenous-1 domain (NC-1) of C7 on skin biopsy, measured by immunofluorescence microscopy (IF) and/or Western blot (WB) analysis
• Presence of ≥100cm2 of blistered and/or erosive skin areas including chronic wounds suitable for skin grafting
• Ability to undergo anaesthesia for skin grafting procedures
• Subjects aged 18 years, willing and able to give informed consent

You may not qualify if:

• Recipients of other investigational medicinal products within 6 months prior to enrolment into this study
• Past medical history of biopsy proven skin malignancy
• 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
• Known allergy to any of the constituents of the investigational medicinal product (IMP) including Penicillin
• 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
• Positive results for HIV, Hepatitis BsAg, Hepatitis BcAb, Hepatitis C IgG, HTLV1\&2 or Syphilis serology
• 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
• Absence of adequate social support
• 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

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Institut Imagine Necker Hospital

Paris, 75743, France

Location

Related Publications (3)

• Gaucher S, Lwin SM, Titeux M, Abdul-Wahab A, Pironon N, Izmiryan A, Miskinyte S, Ganier C, Duchatelet S, Mellerio JE, Bourrat E, McGrath JA, Hovnanian A. EBGene trial: patient preselection outcomes for the European GENEGRAFT ex vivo phase I/II gene therapy trial for recessive dystrophic epidermolysis bullosa. Br J Dermatol. 2020 Mar;182(3):794-797. doi: 10.1111/bjd.18559. Epub 2019 Nov 27. No abstract available.

  PMID: 31557321 BACKGROUND

• Titeux M, Pendaries V, Zanta-Boussif MA, Decha A, Pironon N, Tonasso L, Mejia JE, Brice A, Danos O, Hovnanian A. SIN retroviral vectors expressing COL7A1 under human promoters for ex vivo gene therapy of recessive dystrophic epidermolysis bullosa. Mol Ther. 2010 Aug;18(8):1509-18. doi: 10.1038/mt.2010.91. Epub 2010 May 18.

  PMID: 20485266 BACKGROUND

• Hennig K, Raasch L, Kolbe C, Weidner S, Leisegang M, Uckert W, Titeux M, Hovnanian A, Kuehlcke K, Loew R. HEK293-based production platform for gamma-retroviral (self-inactivating) vectors: application for safe and efficient transfer of COL7A1 cDNA. Hum Gene Ther Clin Dev. 2014 Dec;25(4):218-28. doi: 10.1089/humc.2014.083.

  PMID: 25381930 BACKGROUND

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: December 5, 2019
• Study Start: January 10, 2020
• Primary Completion (Estimated): June 9, 2027
• Study Completion (Estimated): June 9, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

FR (1)