AUTLOGOUS KERATINOCYTES AND FIBROBLASTS TRANSDUCED WITH A RETROVIRAL VECTOR ENCODING COL7A1 CDNA for Recessive dystrophic epidermolysis bullosa (RDEB) | Epidermolysis bullosa

Inclusion criteria

• {"criterion_text":"- 1.≥ 18 year-old\n- 2.Clinical and molecular diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations\n- 3.Significantly reduced staining of C7 on skin biopsy, measured by immunofluorescence microscopy (IF)\n- 4.A reduced number of or morphologically abnormal anchoring fibrils confirmed by TEM\n- 5.Presence of non-collagenous-1 domain (NC-1) of C7 on skin biopsy, measured by immunofluorescence microscopy (IF) and/or Western blot analysis\n- 6.Presence of ≥100cm2 of blistered and/or erosive skin areas including chronic wounds suitable for skin grafting\n- 7.Ability to undergo anaesthesia for grafting procedures\n- 8.Subjects aged ≥ 18years, willing and able to give informed consent"}

Exclusion criteria

• {"criterion_text":"- 1.Recipients of other investigational medicinal products within 6 months prior to enrolment into this study\n- 2.Past medical history of biopsy proven skin malignancy\n- 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\n- 4.Known allergy to any of the constituents of the investigational medicinal product (IMP) including Penicillin\n- 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\n- 6.Positive results for HIV, Hepatitis BsAg, Hepatitis BcAb, Hepatitis C IgG, HTLV1&2 or Syphilis serology\n- 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\n- 8.Absence of adequate social support\n- 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"}

Primary endpoints

• {"endpoint_text":"- Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over a 12-months period after grafting and at each visit during a long term follow-up period of 5 years in total.","definition_or_measurement_approach":"Monitoring and recording of AEs, SAEs, ARs and SARs at each study visit during the 12-month post-grafting period and at each visit during the 5-year long-term follow-up."}

Secondary endpoints

• {"endpoint_text":"- Skin biopsy analysis of grafted skin at, M3, M6, M12, M24, M36, M48 and M60 after grafting compared to baseline for: a)C7 protein expression by immunofluorescence microscopy (IF) b)Morphology of anchoring fibrils (Wetzels et al.) at the dermal-epidermal junction (DEJ) by transmission electron microscopy (TEM)","definition_or_measurement_approach":"Comparison to baseline of C7 protein expression assessed by immunofluorescence microscopy (IF) and morphology of anchoring fibrils analysed by transmission electron microscopy (TEM) at specified timepoints."}
• {"endpoint_text":"- Serum analysis at M1, M6, M12, M18, M24, M30, M36, M42, M48, M54 and M60 after grafting 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","definition_or_measurement_approach":"Serological detection of anti-C7 antibodies using ELISA, IIF and/or Western blot; cellular T-cell responses assessed by ELISPOT at listed timepoints compared to baseline."}
• {"endpoint_text":"- Clinical assessment at M1, M2, M3, M6, M12, M18, M24, M30, M36, M42, M48, M54 and M60 after grafting 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","definition_or_measurement_approach":"Clinical assessments include Vancouver Scar Scale (VSS) for scar quality, blister counts over grafted skin, standardized clinical photography, Leuven Itch Scale (LIS) for pruritus, and QOLEB for quality of life at specified visits compared to baseline."}

France

Earliest CTIS Part Ii Submission Date

23-01-2025

Latest Decision Or Authorization Date

29-01-2025

Processing Time Days

6

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Institut National De La Sante Et De La Recherche Medicale

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Cure EB","duties_or_roles":"Source of monetary support","organisation_type":""}