Safety Study of Gene-modified Autologous Fibroblasts in Recessive Dystrophic Epidermolysis Bullosa

Phase 1

Completed

• Conditions: Recessive Dystrophic Epidermolysis Bullosa
• Interventions: Drug: Gene-modified autologous fibroblasts

• Registration Number: NCT02493816
• Lead Sponsor: King's College London

Brief Summary

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.

Detailed Description

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of blistering skin disease caused by mutations in COL7A1 gene. This study aims to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.

This is an open-label single-centre phase I study with primary objective to evaluate the adverse and serious adverse events over 12 months' follow-up period. Secondary objectives include (1) analysis of type VII collagen (C7) expression and morphology of anchoring fibrils in the injected areas of the skin; (2) analysis of immune response to newly expressed C7.

Each study participant will receive three intradermal injections of COL7A1 gene-modified autologous fibroblasts on Day 0 only. Each subject will undergo an initial screening including a physical examination and assessment of disease severity. Blood analyses and skin biopsies will be performed at various time points as per the monitoring schedule over 12 months.

Study Timeline

• Study First Submitted: 2015-05-21
• Study First Submitted QC: 2015-07-07
• Study First Posted: 2015-07-10
• Study Start: 2015-09
• Primary Completion: 2018-03
• Study Completion: 2018-03
• Status Verified: 2018-08
• Last Update Submitted: 2019-09-20
• Last Update Posted: 2019-09-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

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 5x8cm of intact skin on the trunk and/or extremities that is suitable for cell injections.
4. Able to undergo local anaesthesia.
5. Subjects aged ≥ 17 years and able to give informed consent prior to the first study intervention.

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 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.

7. Subjects with positive results for HIV, Hepatitis B, Hepatitis C, HTLV or Syphilis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gene-modified autologous fibroblasts	Gene-modified autologous fibroblasts	3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.

Primary Outcome Measures

Name	Time	Method
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period.	12 months

Secondary Outcome Measures

Name	Time	Method
Vector copy number, measured by q-PCR, in the treated and untreated skin	Week 2, Month 3 and Month 12
T-cell responses to full length type VII collagen measured by ELISPOT	Week 2, Month 1, Month 3, Month 6 and Month 12
Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence	Week 2, Month 1, Month 3, Month 6 and Month 12
Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin	Week 2, Month 3 and Month 12
Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin	Week 2, Month 3 and Month 12

Trial Locations

Locations (1)

Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom