Gene Therapy Trial in adults with Inherited Blistering Skin Disease

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2014-004884-19-GB
• Date of registration: 18/02/2015
• Prospective Registration: Yes
• Primary sponsor: King's College London
• Public title: Gene Therapy Trial in adults with Inherited Blistering Skin Disease
• Scientific title: Phase I study of lentiviral-mediated COL7A1 gene-modified autologous fibroblasts in adults with recessive dystrophic epidermolysis bullosa (RDEB) - LENTICOL-F
• Date of first enrolment: 24/05/2016
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004884-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Professor John A McGrath
• Affiliation: King's College London and Guy's and St Thomas' NHS Foundation Trust

• Name: Professor John A McGrath
• Affiliation: King's College London and Guy's and St Thomas' NHS Foundation Trust

Key inclusion & exclusion criteria

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Recessive Dystrophic Epidermolysis Bullosa
MedDRA version: 18.1 Level: PT Classification code 10014989 Term: Epidermolysis bullosa System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

Intervention(s)

Product Name: SIN LV Mediated ex vivo transduced autologous fibroblasts expressing codon-optimised COL7A1
Product Code: Not applicable
Pharmaceutical Form: Suspension for injection in pre-filled syringe

Primary Outcome(s)

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.

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.

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.

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,

Main Objective: To evaluate the safety of intradermal injections of SIN LV-mediated COL7A1 gene-modified autologous fibroblasts in adults with RDEB.

Secondary Outcome(s)

Secondary end point(s): Skin biopsy analysis of treated skin at W2, M3 and M12 compared to untreated skin:

I. C7 protein expression by immunofluorescence microscopy (IF)
II. Morphology of anchoring fibrils at the dermal-epidermal junction (DEJ) by transmission electron microscopy (TEM)
III. Vector copy number by quantitative polymerase chain reaction (qPCR)
? Serum analysis for:
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
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.

Secondary ID(s)

LENTICOL-F

Source(s) of Monetary Support

Sohana Research Fund

DebRA International

Secondary Sponsor(s)

Guy's and St Thomas' NHS Foundation Trust