A prospective phase I/II study to evaluate allogeneic mesenchymal stromal cells for the treatment of skin disease in children with recessive dystrophic epidermolysis bullosa.

• Register: EUCTR
• Last refreshed on: 4 December 2018
• Main ID: EUCTR2012-001394-87-GB
• Date of registration: 22/08/2012
• Prospective Registration: Yes
• Primary sponsor: King's College London
• Public title: A prospective phase I/II study to evaluate allogeneic mesenchymal stromal cells for the treatment of skin disease in children with recessive dystrophic epidermolysis bullosa.
• Scientific title: A prospective phase I/II study to evaluate allogeneic mesenchymal stromal cells for the treatment of skin disease in children with recessive dystrophic epidermolysis bullosa. - EBSTEM
• Date of first enrolment: 16/11/2012
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001394-87
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• 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: Dept of Genetics and Molecular Med.
• Affiliation: Prof. John A. McGrath

• Name: Dept of Genetics and Molecular Med.
• Affiliation: Prof. John A. McGrath

Key inclusion & exclusion criteria

Inclusion criteria:
1) Subjects who have a diagnosis of recessive dystrophic epidermolysis bullosa (RDEB) characterised by partial or complete C7 deficiency.
2) Subjects who are = 12 months and = 17 years of age at the time of enrolment.
3) Subjects whose responsible parent/guardian has voluntarily signed and dated an Informed Consent Form (ICF) prior to the first study intervention. Whenever the minor child is able to give consent, the minor’s assent will be obtained in addition to the signed consent of the minor’s legal guardian.

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects will be excluded from the study if ANY of the following conditions exist:
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) or chemotherapy within 60 days of enrolment into this study.
3) Subjects with a known allergy to any of the constituents of the investigational product.
4) Subjects with signs of active infection.
5) Subjects with a medical history or evidence of malignancy, including cutaneous squamous cell carcinoma.
6) Subjects with both a) positive C7 ELISA and b) a positive indirect immunofluorescence (IIF) with binding to the base of salt split skin.
7) 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.



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

Health Condition(s) or Problem(s) studied

Recessive Dystrophic Epidermolysis Bullosa
MedDRA version: 17.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders

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

Intervention(s)

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

Primary Outcome(s)

Secondary Objective: • Incidence of infusional toxicity.
• Increase in C7 deposition at the DEJ post treatment at D0 and D60.
• Quantitative analysis of the donor cells chimerism at D60.
• Improvement of haematological and serological markers of generalised inflammation at D0, D7, D28, D60 and D180 compared to baseline.
• Improvement in the clinical appearances of the skin.
• Improved quality of life according to validated paediatric QoL scoring systems at screening, D60, D100 and D180.
• Pain scoring at screening, D0, D7, D28, D60, D100 and D180.
• Reduction in blister occurrence over entire body surface at D0, D7, D28, D60, D100 and D180 as compared to baseline.
• Increase in skin strength measured by time to blister formation after skin suction at screening and D100.

Timepoint(s) of evaluation of this end point: at every visit up to 12-months after last IMP infusion

Main Objective: To evaluate the safety of allogeneic intravenously administered MSCs in children with RDEB over a 24-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 12-month follow-up period. SAEs are defined as any occurrences related to the administration of the IMP that result in death, or is life-threatening or requires hospitalisation or prolongation of existing hospitalisation.

Secondary Outcome(s)

Secondary end point(s): •Incidence of infusional toxicity.
•Increase in collagen VII deposition at the DEJ post treatment.
•Quantitative analysis of the donor cells dermal chimerism.
•Improvement of haematological and serological markers of generalised inflammation.
•General clinical appearance of the skin based on medical photographs, generalised severity score and BEBSS score.
•Improved quality of life.
•Pain scoring.
•Reduction in blister numbers.
•Increase in skin strength measured by increased time to blister formation after skin suction

Timepoint(s) of evaluation of this end point: •toxicity 1 hour post infusion
•Increase in collagen VII deposition at the DEJ post treatment at Day 0 and D60
•Quantitative analysis of the donor cells dermal chimerism at Day 60
•Improvement of markers of generalised inflammation at D0, D7, D28, D60 and D180
•General clinical appearance of the skin based on medical photographs on each visit
•Improved quality of life according to validated paediatric QoL scoring systems at screening, D60, D100 and D180
•Pain scoring at screening, D0, D7, D28, D60, D100 and D180
•Reduction in blister occurrence over entire body surface at D0, D7, D28, D60, D100 and D180 as compared to baseline
•Increase in skin strength measured by time to blister formation after skin suction at screening and D100

Secondary ID(s)

EBSTEM001

Source(s) of Monetary Support

Dystrophic Epidermolysis Bullosa Research Association