Safety study of mesenchymal stem cells in the treatment of Recessive Dystrophic Epidermolysis Bullosa.

• Register: EUCTR
• Last refreshed on: 26 February 2018
• Main ID: EUCTR2017-000606-37-ES
• Date of registration: 18/09/2017
• Prospective Registration: Yes
• Primary sponsor: Fundación para la Investigación Biomédica Hospital Universitario La Paz
• Public title: Safety study of mesenchymal stem cells in the treatment of Recessive Dystrophic Epidermolysis Bullosa.
• Scientific title: Safety and preliminary efficacy study of infusing mesenchymal stem cells derived from bone marrow for treating Recessive Dystrophic Epidermolysis Bullosa.
• Date of first enrolment: 16/11/2017
• Target sample size: 9
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000606-37
• 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; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: UCICEC
• Affiliation: Hospital Universitario La Paz

• Name: UCICEC
• Affiliation: Hospital Universitario La Paz

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients = 4 and = 18 years old at the time of inclusion in the study.
2. Patients with clinical, molecular and genetic diagnosis of EBDR.
3. Patients with presence of the NC-1 domain of type VII collagen in skin and/or western blot biopsies detected with a battery of specific antibodies
4. Patients with haploidentical donor
5. Subjects with a severity score of> 20 according to "The Birmingham Epidermolysis Bullosa Severity Score".
6. Minors whose legal representative / guardian has voluntarily signed informed consent prior to the first study intervention.
7. In the case of mature minors (12-17 years of age), in addition to the consent signed by the legal guardian, the child's consent will be obtained.
8. Women with reproductive capacity should have a negative pregnancy test at the time of inclusion and must have access to highly effective contraceptive methods (diaphragms plus spermicide or male condom plus spermicide, oral contraceptive combined with a second contraceptive implant method, contraceptive Injecting, permanent intrauterine device, sexual abstinence or partner with vasectomy) during their participation in the study and in the 30 following the last visit.
9. Males should agree to use a double barrier contraceptive method (condom plus spermicide or diaphragm plus spermicide) during their participation in the study and 30 days after the last dose of the study drug, or the male patient or their Female couple should be surgically sterilized or the female partner should be postmenopausal.
10. The patient should be able to attend all study visits and follow all study procedures.
Are the trial subjects under 18? yes
Number of subjects for this age range: 9
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:
1. Subjects that for medical reasons can not be transferred to La Paz University Hospital in Madrid.
2. Subjects who have received immunotherapy, including oral corticosteroids (> 15 mg / day) for more than 1 week (except for intranasal and topical preparations) or chemotherapy within 8 days prior to inclusion in the study. Inclusion of the patient is understood from the signing of informed consent.
3. Subjects with a known allergy to any component of the product under investigation (including penicillin and streptomycin), or who can not receive antihistamine and / or corticoid treatment.
4. Subjects with signs of active systemic infection at the time of inclusion in the study.
5. Subjects with a history or signs of malignancy, including cutaneous squamous cell carcinoma.
6. Subjects with circulating anti-C7 antibodies and anti-C7 antibodies deposited at the dermoepidermal junction detected in skin biopsies by indirect immunofluorescence.
7. Pregnant women at the time of inclusion or women of childbearing age who do not practice abstinence or use acceptable means of contraception, as determined by the investigator during the trial.
8. Biochemical abnormalities at the time of inclusion: albumin <2.5 g / dL, Hemoglobin <7.5 g / dL.
9. Subjects who have been given other investigational drugs within 90 days prior to the treatment phase.
10. Subjects who are not able to understand the information sheet and are unable to sign informed consent.


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: Mesenchymal Stem Cells extracted from bone marrow
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Células madre mesenquimales haploidénticas derivadas de médula ósea
Current Sponsor code: MSCs
Other descriptive name: MESENCHYMAL STEM CELLS (MSCS)
Concentration unit: Other
Concentration type: range
Concentration number: 2000000-4000000

Primary Outcome(s)

Secondary Objective: • To describe the clinical and molecular phenotype of the muco-cutaneous involvement of patients, including the characterization of the mutations responsible for the disease.

• Evaluate the preliminary efficacy of treatment with haploidentical Mesenchymal Stem Cells derived from bone marrow given by intravenous injection in 3 infusions of 2-4 x 10e6 cells/kg each separated by 21 days for the treatment of patients with EBDR. The evaluation of the symptomatic improvement of the treated patients will be made regarding the baseline situation and the response to treatment at biochemical, histological and molecular level.

Main Objective: • Assessing the safety of haploidentical Mesenchymal Stem Cells derived from bone marrow given by intravenous injection with a dose of 2-4 x 10e6 cells/kg in 3 separate infusions for 21 days each for the treatment of patients with Recessive Dystrophic Epidermolysis Bullosa.

Primary end point(s): Safety assessment: Proportion of adverse events over a period of 12 months after treatment. The type, duration, intensity, severity and causal relationship with the treatment of adverse events shall be recorded. Safety assessments will include active interrogation of adverse events, physical, analytical and molecular examination. A long-term clinical follow-up of at least 5 years after completion of study medication will be included as part of the care activity in order to primarily monitor the occurrence of cutaneous squamous cell carcinoma.

Timepoint(s) of evaluation of this end point: 12 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 12 months.

Secondary end point(s): • Cutaneous mechanical resistance measured using a negative pressure cutaneous suction device from Electronic Diversities (model NP-2). The mechanical resistance will be determined as the minimum time required to induce a 5 mm diameter ampulla at a constant pressure in the forearm of the subject.
• Percentage of skin surface affected
• Evaluation of the number of blisters.
• Improvement of hematological and serological markers of generalized inflammation.
• Severity Score according to "The Birmingham Epidermolysis Bullosa Severity Score" and "The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI)" before and after treatment.
• Expression of Collagen VII (C7) in cutaneous biopsy before and after infusion of MSCs.
• Analysis of anchor fibrils by electron microscopy in skin biopsy after treatment.
• Variation of pain with respect to baseline that will be assessed by the Visual Analogue Scale (EVA) at all visits following the first infusion.
• Assessment of the change in perceived itching from baseline that will be assessed by Leuven Itch Scale at all visits after the first infusion.
• Assessment of change in quality of life: a specific quality of life assessment survey (European Quality of Life-5 Dimensions-5 level). The survey will be conducted before treatment and at all follow-up visits.
• Analysis of circulating anti-C7 antibodies determined by ELISA before and after treatment.
• Analysis of detectable levels of anti-C7 antibodies in the dermo-epidermal junction by indirect immunofluorescence before (exclusion criterion) and after treatment.
• Assessment of the general condition of the patient. To do this, each visit to the patient and the doctor will be surveyed by recording the overall assessment using a Likert scale.
• Analysis of pro-inflammatory cytokines before and after infusion of MSCs.
• Presence of donor cells (dermal chimerism).

Secondary ID(s)

MesenSistem-EB

Source(s) of Monetary Support

Ministerio de Economía y Competitividad