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

Recessive Dystrophic Epidermolysis Bullosa Clinical Trial

Official title:

Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02493816
• Other study ID #: LENTICOL-F
• Status: Completed
• Phase: Phase 1
• Start date: September 2015
• Est. completion date: March 2018

Study information

• Verified date: August 2018
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Epidermolysis Bullosa Dystrophica
• Recessive Dystrophic Epidermolysis Bullosa

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
King's College London	University College, London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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, — View Citation

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. — View Citation

Outcome

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