Mesenchymal Stromal Cells in Adults With Recessive Dystrophic Epidermolysis Bullosa (ADSTEM)

• ClinicalTrials.gov Identifier: NCT02323789
• Recruitment Status: Unknown
• First Posted: December 23, 2014
• Last Update Posted: March 3, 2017
• Sponsor: King's College London
• Information provided by (Responsible Party): King's College London

Study Description

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

Condition or disease	Intervention/treatment	Phase
Recessive Dystrophic Epidermolysis Bullosa	Drug: Mesenchymal stromal cells	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase I/II Study Evaluating Allogeneic Mesenchymal Stromal Cells in Adults With Recessive Dystrophic Epidermolysis Bullosa
• Actual Study Start Date: June 2015
• Estimated Primary Completion Date: July 2017
• Estimated Study Completion Date: July 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention arm; 10 patients with RDEB will be selected to receive the intervention - mesenchymal stromal cells.	Drug: Mesenchymal stromal cells; TC-MSC: a cell product containing mesenchymal stromal cells. Mesenchymal stromal cells are adherent non-haematopoietic multipotent cells that are expanded from bone marrow from healthy donors, using platelet lysate as source of growth factor.; Other Name: TC-MSC

Outcome Measures

Primary Outcome Measures :

1. Lack of serious and severe adverse events (SAEs) related to the administration of the investigational medicinal product. [ Time Frame: 12 months ]

Secondary Outcome Measures :

1. Presence of new type VII collagen at the dermal-epidermal junction post treatment. [ Time Frame: Day 14, Day 28, Day 60, Day 100 and Month 6. ]
2. Change in general markers of inflammation [ Time Frame: Day 14, Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline ]
3. Changes in specific markers of inflammation [ Time Frame: Day 14, Day 28, Day 60 and Month 6 compared to baseline ]
4. Change in the clinical changes in the skin assessed with clinical photographs [ Time Frame: Day 14, Day 28, Day 60, Day 100, Month 6 and Month 12. ]
5. Differences in quality of life data [ Time Frame: Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline ]
6. Change in BEBSS and EBDASI scores [ Time Frame: at Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline ]
7. Change in Pain scores [ Time Frame: Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline ]
8. Change in pruritus score using the Leuven Itch Scale (LIS) [ Time Frame: Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline. ]
9. Quantification of total blister numbers over the entire body surface area [ Time Frame: Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline ]
10. 10. Increase in the skin strength measured by time to blister formation after negative pressure skin suction test [ Time Frame: Day 28, Day 60, Day 100, Month 6 and Month 12 compared to baseline ]
11. Qualitative analyses based on a series of interview questions [ Time Frame: between 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United Kingdom

Guys and St Thomas' hospital NHS Trust

London, United Kingdom, SE1 9RT

Sponsors and Collaborators

King's College London

Investigators

• Principal Investigator: John McGrath, FRCP/FSci/MD; King's College London

More Information

• Responsible Party: King's College London
• ClinicalTrials.gov Identifier: NCT02323789
• Other Study ID Numbers: ADSTEM001
• First Posted: December 23, 2014
• Last Update Posted: March 3, 2017
• Last Verified: March 2017

Additional relevant MeSH terms:

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