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

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ClinicalTrials.gov Identifier: NCT02493816
Recruitment Status : Completed
First Posted : July 10, 2015
Last Update Posted : August 9, 2018
Sponsor:
Collaborator:
University College, London
Information provided by (Responsible Party):
King's College London

Study Description
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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.

Condition or disease Intervention/treatment Phase
Recessive Dystrophic Epidermolysis Bullosa Drug: Gene-modified autologous fibroblasts Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults With Recessive Dystrophic Epidermolysis Bullosa.
Actual Study Start Date : September 2015
Actual Primary Completion Date : March 2018
Actual Study Completion Date : March 2018

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Gene-modified autologous fibroblasts
3 intradermal injections of COL7A1 gene-modified autologous fibroblasts will be administered on day 0 only.
 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


Outcome Measures
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Primary Outcome Measures :
  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. [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Type VII collagen protein expression, measured by direct immunofluorescence, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
  2. Morphology of anchoring fibrils, measured by transmission electron microscopy, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
  3. Vector copy number, measured by q-PCR, in the treated and untreated skin [ Time Frame: Week 2, Month 3 and Month 12 ]
  4. Anti-type VII collagen antibodies measured by ELISA and indirect immunofluorescence [ Time Frame: Week 2, Month 1, Month 3, Month 6 and Month 12 ]
  5. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02493816


Locations
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United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
King's College London
University College, London
Investigators
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Principal Investigator: John A McGrath, FRCP King's College London
More Information
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Publications:

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Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT02493816     History of Changes
Other Study ID Numbers: LENTICOL-F
First Posted: July 10, 2015    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
 Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Collagen Diseases
Connective Tissue Diseases