A prospective phase I/II study to evaluate the use of mesenchymal stromal (stem) cells for the treatment of skin disease in adults with recessive dystrophic epidermolysis bullosa

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2014-004500-30-GB
• Date of registration: 22/12/2014
• Prospective Registration: Yes
• Primary sponsor: King's College London
• Public title: A prospective phase I/II study to evaluate the use of mesenchymal stromal (stem) cells for the treatment of skin disease in adults with recessive dystrophic epidermolysis bullosa
• Scientific title: A phase I/II study evaluating allogeneic mesenchymal stromal cells in adults with recessive dystrophic epidermolysis bullosa - ADSTEM
• Date of first enrolment: 13/02/2015
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004500-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Professor John A. McGrath
• Affiliation: Guy's and St Thomas NHS Foundation Trust and King's College London

• Name: Professor John A. McGrath
• Affiliation: Guy's and St Thomas NHS Foundation Trust and King's College London

Key inclusion & exclusion criteria

Inclusion criteria:
1) Individuals with a diagnosis of RDEB confirmed by DNA analysis .
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.
6) Subjects with both a) positive C7 ELISA and b) a positive indirect immunofluorescence (IIF) with binding to the base of salt split skin.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Recessive dystrophic epidermolysis bullosa

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: Allogeneic mesenchymal stromal cells
Product Code: TC-MSC
Pharmaceutical Form: Injection

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At every visit over a 12 month period for first 8 subjects and over 8 months for the final two subjects.

Secondary Objective: 1. Presence of new type VII collagen at the dermal-epidermal junction post treatment
2. Changes in general markers of inflammation
3.Changes in specific markers of inflammation using ELISA and LUMINEX platforms
4.Changes in the clinical appearance of the skin
5.Changes in BEBSS and EBDASI scores
6.Change in Quality of Life Score using the QOLEB questionnaire.
7.Change in pruritus score using the Leuven Itch Scale (LIS)
8. Quantification of total blister numbers over the entire body surface area.
9.Increase in the skin strength measured by time to blister formation after negative pressure skin suction test

Main Objective: To evaluate the safety of allogeneic intravenously administered MSCs in adults with RDEB over a 8 or a 12-month period.

Primary end point(s): Lack of serious and severe adverse events (SAEs) related to the administration of the investigational medicinal product over a 8 or a 12 month period. SAEs are defined as any occurrence related to the administration of the IMP that results in death, or is life threatening or requires hospitalization or prolongation of existing hospitalization.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: As above

Secondary end point(s): 1. Presence of new type VII collagen at the dermal-epidermal junction post treatment on Day 28, Day 60, and Month 6.
2. Changes in general markers of inflammation at Day 14, Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
3. Changes in specific markers of inflammation on Day 14, Day 28, Day 60 and Month 6 compared to baseline using ELISA and LUMINEX platforms. Specific inflammatory markers include: HMGB-1, TNF a, IFN ?, IL-17A, IL1 ß, IL-10, MMP-2, MMP-9, MMP-11 and TIMP-1.
4. Changes in the clinical appearance of the skin assessed with clinical photographs.
5. Differences in quality of life data at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
6. Changes in BEBSS and EBDASI scores at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline. 7. Change in pruritus score using the Leuven Itch Scale (LIS) at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
8. Quantification of total blister numbers over the entire body surface area at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.
9. Increase in the skin strength measured by time to blister formation after negative pressure skin suction test at Day 28, Day 60, Day 100, Month 6 (for all patients) and Month 12 (for the first eight eligible patients) or Month 8 (for the last two eligible patients) compared to baseline.

Secondary ID(s)

ADSTEM001

Source(s) of Monetary Support

Dystrophic Epidermolysis Bullosa Research Association

Dystrophic Epidermolysis Bullosa Research Association

Secondary Sponsor(s)

Guy's and St Thomas NHS Foundation Trust

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 28/02/2019
• Date Completed: 10/10/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004500-30/results