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Mesenchymal Stromal Cells in Adults With Recessive Dystrophic Epidermolysis Bullosa

Phase 1
Conditions
Recessive Dystrophic Epidermolysis Bullosa
Interventions
Registration Number
NCT02323789
Lead Sponsor
King's College London
Brief Summary

To assess whether intravenously administered third-party bone marrow-derived mesenchymal stromal cells (MSCs) are safe and have an impact on disease severity in RDEB

Detailed Description

This is a phase I/II clinical trial with a key objective of evaluating safety of third party bone MSCs intravenous infusions in 10 adults with the inherited severe skin fragility disorder, recessive dystrophic epidermolysis bullosa (RDEB). The main objectives of our study are to: (1) to assess the spectrum of clinical responses in adults with RDEB receiving intravenous MSCs; (2) to identify the best cohort of individuals to target for future trials and therapies; (3) to improve our understanding of in vivo and in vitro responsiveness to MSCs; (4) to identify candidate molecules germane to activating MSCs and making them clinically more potent, independently of the permissive conditions of the patient and (5) to assess its impact on reducing disease morbidity/severity in this population.

This is a prospective, non-randomised, open label study. All study participants will receive two intravenous MSC infusions at baseline Day 0 and Day 14 and will be followed up for a 12 month period following the first infusion. Each subject will undergo an initial screening including physical examination, assessment of vital signs and disease severity assessment.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
10
Inclusion Criteria
  1. Individuals with a diagnosis of RDEB confirmed by DNA analysis and skin immunofluorescence for partial or complete absence of type VII collagen.
  2. Individuals ≥ 18 years and ≤ 65 years of age, both male and female
  3. Individuals that have voluntarily signed and dated an informed consent form (ICF) prior to the first study intervention.
Exclusion Criteria
  1. Subjects who have had other investigational medicinal products within 90 days prior to screening or during the treatment phase.
  2. Subjects who have received immunotherapy including oral corticosteroids for more than 1 week (intranasal and topical preparations are permitted).
  3. Subjects with a known allergy to any of the constituents of the investigational product.
  4. Subjects with a medical history or evidence of malignancy, including cutaneous squamous cell carcinoma.
  5. Subjects who are pregnant or of child-bearing potential who are not abstinent or practicing an acceptable means of contraception, as determined by the Investigator, for the duration of the treatment phase.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Intervention armMesenchymal stromal cells10 patients with RDEB will be selected to receive the intervention - mesenchymal stromal cells.
Primary Outcome Measures
NameTimeMethod
Lack of serious and severe adverse events (SAEs) related to the administration of the investigational medicinal product.12 months
Secondary Outcome Measures
NameTimeMethod
Change in general markers of inflammationDay 14, Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline
Differences in quality of life dataDay 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline
Presence of new type VII collagen at the dermal-epidermal junction post treatment.Day 14, Day 28, Day 60, Day 100 and Month 6.
Quantification of total blister numbers over the entire body surface areaDay 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline
Change in the clinical changes in the skin assessed with clinical photographsDay 14, Day 28, Day 60, Day 100, Month 6 and Month 12.
Change in BEBSS and EBDASI scoresat Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline
Change in Pain scoresDay 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline
Change in pruritus score using the Leuven Itch Scale (LIS)Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline.
Changes in specific markers of inflammationDay 14, Day 28, Day 60 and Month 6 compared to baseline
10. Increase in the skin strength measured by time to blister formation after negative pressure skin suction testDay 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline
Qualitative analyses based on a series of interview questionsbetween screening and Day 0, between Day 28 and Day 60, and between Month 6 and Month 12.

to reveal objective data on quality of sleep, skin healing time, amount of dressings used, improvement in oral diet, improvement in energy levels, mood, quality of family life/relationships.

Trial Locations

Locations (1)

Guys and St Thomas' hospital NHS Trust

🇬🇧

London, United Kingdom

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