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Trial record 1 of 1 for:    02493816
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Safety Study of Gene-modified Autologous Fibroblasts in Recessive Dystrophic Epidermolysis Bullosa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02493816
Recruitment Status : Completed
First Posted : July 10, 2015
Last Update Posted : September 24, 2019
Sponsor:
Collaborator:
University College, London
Information provided by (Responsible Party):
King's College London

Tracking Information
First Submitted Date  ICMJE May 21, 2015
First Posted Date  ICMJE July 10, 2015
Last Update Posted Date September 24, 2019
Actual Study Start Date  ICMJE September 2015
Actual Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 7, 2015)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02493816 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2015)
  • Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
  • Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
  • Vector copy number, measured by q-PCR, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
  • Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence [ Time Frame: Week 2, Month 1, Month 3, Month 6 and Month 12 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Gene-modified Autologous Fibroblasts in Recessive Dystrophic Epidermolysis Bullosa
Official Title  ICMJE Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recessive Dystrophic Epidermolysis Bullosa
Intervention  ICMJE Drug: Gene-modified autologous fibroblasts
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
Other Name: COL7A1 gene-modified autologous fibroblasts
Study Arms  ICMJE Experimental: Gene-modified autologous fibroblasts
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
Intervention: Drug: Gene-modified autologous fibroblasts
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 19, 2018)
5
Original Estimated Enrollment  ICMJE
 (submitted: July 7, 2015)
10
Actual Study Completion Date  ICMJE March 2018
Actual Primary Completion Date March 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 17 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02493816
Other Study ID Numbers  ICMJE LENTICOL-F
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party King's College London
Study Sponsor  ICMJE King's College London
Collaborators  ICMJE University College, London
Investigators  ICMJE
Principal Investigator: John A McGrath, FRCP King's College London
PRS Account King's College London
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP