Gene Therapy Trial in adults with Inherited Blistering Skin Disease

Phase 1

Conditions: Recessive Dystrophic Epidermolysis Bullosa
MedDRA version: 18.1Level: PTClassification code 10014989Term: Epidermolysis bullosaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2014-004884-19-GB

Lead Sponsor: King's College London

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 10

Inclusion Criteria

1. Clinical and genetic diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations.
2. A reduced number or morphologically abnormal anchoring fibrils confirmed by TEM.
3. At least 5x3cm of intact skin on the trunk and/or extremities that is suitable for cell injections.
4. Able to undergo local anaesthesia.
5. Subjects aged = 17years and able to give informed consent prior to the first study intervention.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects who received other investigational medicinal products within 6 months prior to enrolment into this study.
2. Past medical history of biopsy proven skin malignancy.
3. Subjects who have received 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).
5. Subjects with BOTH:
? - positive serum antibodies to C7 confirmed by ELISA and
? - positive IIF with binding to the base of salt split skin.
6. Subjects with positive results for HIV, Hepatitis B, Hepatitis C, HTLV or Syphilis.
7. Subjects who are pregnant or of child-bearing potential who are neither abstinent nor practising 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 12 months after the cell injections.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of intradermal injections of SIN LV-mediated COL7A1 gene-modified autologous fibroblasts in adults with RDEB.;Secondary Objective: 1. To evaluate the potential efficacy of intradermal injections of SIN LV-mediated COL7A1 gene-modified autologous fibroblasts in adults with RDEB at week (W) 2, month (M) 3 and M12 after the IMP injections.<br><br>2. To evaluate the immune response against the recombinant type VII collagen (C7) at W2, W4, M3, M6 and M12 after the IMP injections compared to baseline.;Primary end point(s): Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit after screening over a 12 month follow up period.;Timepoint(s) of evaluation of this end point: At every visit over a 12 month period post IMP administration. Trial visits are scheduled at Week 1, Week 2, Week 4 , Month 3, Month 6, Month 9, Month 12,

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Skin biopsy analysis of treated skin at W2, M3 and M12 compared to untreated skin:<br><br>I. C7 protein expression by immunofluorescence microscopy (IF)<br>II. Morphology of anchoring fibrils at the dermal-epidermal junction (DEJ) by transmission electron microscopy (TEM)<br>III. Vector copy number by quantitative polymerase chain reaction (qPCR)<br>? Serum analysis for:<br>IV. Detection of anti-C7 antibodies by enzyme-linked immunosorbent assay (ELISA) (against NC1 and NC2 domains of C7) and indirect immunofluorescence (IIF) at W2, W4, M1, M3, M6 and M12 post-injections<br>V. Detection of T-cell responses to the full length C7 by enzyme-linked immunosorbent spot (ELISPOT) assay at W4, M6 and M12 post-injections.;Timepoint(s) of evaluation of this end point: At the above specified visits over a 12 month follow up period post IMP administration.