search
Back to results

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

Primary Purpose

Recessive Dystrophic Epidermolysis Bullosa

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Gene-modified autologous fibroblasts
Sponsored by
King's College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recessive Dystrophic Epidermolysis Bullosa

Eligibility Criteria

17 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Guy's and St Thomas' NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gene-modified autologous fibroblasts

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
May 21, 2015
Last Updated
September 20, 2019
Sponsor
King's College London
Collaborators
University College, London
search

1. Study Identification

Unique Protocol Identification Number
NCT02493816
Brief Title
Safety Study of Gene-modified Autologous Fibroblasts in Recessive Dystrophic Epidermolysis Bullosa
Official Title
Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
September 2015 (Actual)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
King's College London
Collaborators
University College, London

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recessive Dystrophic Epidermolysis Bullosa

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gene-modified autologous fibroblasts
Arm Type
Experimental
Arm Description
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
Intervention Type
Drug
Intervention Name(s)
Gene-modified autologous fibroblasts
Other Intervention Name(s)
COL7A1 gene-modified autologous fibroblasts
Intervention Description
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
Primary Outcome Measure Information:
Title
Adverse events (AEs), Serious Adverse Events (SAEs), Adverse Reactions (ARs) and Serious Adverse Reactions (SARs) at each visit over 12 months' follow up period.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin
Time Frame
Week 2, Month 3 and Month 12
Title
Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin
Time Frame
Week 2, Month 3 and Month 12
Title
Vector copy number, measured by q-PCR, in the treated and untreated skin
Time Frame
Week 2, Month 3 and Month 12
Title
Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence
Time Frame
Week 2, Month 1, Month 3, Month 6 and Month 12
Title
T-cell responses to full length type VII collagen measured by ELISPOT
Time Frame
Week 2, Month 1, Month 3, Month 6 and Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John A McGrath, FRCP
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18385758
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.
Results Reference
background
PubMed Identifier
31167965
Citation
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs