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

NCT02493816 | Completed Phase 1 DMC

• 1 other identifier: LENTICOL-F
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• Vector copy number, measured by q-PCR, in the treated and untreated skin

  Week 2, Month 3 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

• T-cell responses to full length type VII collagen measured by ELISPOT

  Week 2, Month 1, Month 3, Month 6 and Month 12

Study Arms (1)

Gene-modified autologous fibroblasts

EXPERIMENTAL

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

Drug: Gene-modified autologous fibroblasts

Interventions

Gene-modified autologous fibroblasts DRUG

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

Also known as: COL7A1 gene-modified autologous fibroblasts

Gene-modified autologous fibroblasts

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical and genetic diagnosis of RDEB with confirmed bi-allelic COL7A1 mutations.
• A reduced number or morphologically abnormal anchoring fibrils confirmed by TEM.
• At least 5x8cm of intact skin on the trunk and/or extremities that is suitable for cell injections.
• Able to undergo local anaesthesia.
• Subjects aged ≥ 17 years and able to give informed consent prior to the first study intervention.

You may not qualify if:

• Subjects who received other investigational medicinal products within 6 months prior to enrolment into this study.
• Past medical history of biopsy proven skin malignancy.
• 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.
• Known allergy to any of the constituents of the investigational medicinal product (IMP).
• Subjects with BOTH:
• positive serum antibodies to C7 confirmed by ELISA and
• positive IIF with binding to the base of salt split skin.
• 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.
• Subjects with positive results for HIV, Hepatitis B, Hepatitis C, HTLV or Syphilis.

Sponsors & Collaborators

• King's College London: lead
• University College, London: collaborator

Study Sites (1)

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Related Publications (2)

• Wong T, Gammon L, Liu L, Mellerio JE, Dopping-Hepenstal PJ, Pacy J, Elia G, Jeffery R, Leigh IM, Navsaria H, McGrath JA. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2008 Sep;128(9):2179-89. doi: 10.1038/jid.2008.78. Epub 2008 Apr 3.

  PMID: 18385758 BACKGROUND

• Lwin SM, Syed F, Di WL, Kadiyirire T, Liu L, Guy A, Petrova A, Abdul-Wahab A, Reid F, Phillips R, Elstad M, Georgiadis C, Aristodemou S, Lovell PA, McMillan JR, Mee J, Miskinyte S, Titeux M, Ozoemena L, Pramanik R, Serrano S, Rowles R, Maurin C, Orrin E, Martinez-Queipo M, Rashidghamat E, Tziotzios C, Onoufriadis A, Chen M, Chan L, Farzaneh F, Del Rio M, Tolar J, Bauer JW, Larcher F, Antoniou MN, Hovnanian A, Thrasher AJ, Mellerio JE, Qasim W, McGrath JA. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. JCI Insight. 2019 Jun 6;4(11):e126243. doi: 10.1172/jci.insight.126243. eCollection 2019 Jun 6.

  PMID: 31167965 RESULT

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 Officials

• John A McGrath, FRCP

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: July 10, 2015
• Study Start: September 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: September 24, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)