Safety and Efficacy of ADSTEM Inj. in Patients With Moderately Subacute and Chronic Atopic Dermatitis

Study Overview
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Brief Summary
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This study aims to evaluate safety, tolerance, and efficacy in subjects with over moderately subacute and chronic atopic dermatitis after an intravenous injection of autologous mesenchymal stem cells. The study is composed of two steps. Step 1 is to determine clinically proper dose capacity of the ADSTEM Inj. and step 2 is to evaluate exploratory efficacy of the ADSTEM Inj. at the proper dose.

Detailed Description
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Atopic dermatitis (AD) is a type of inflammation of the skin. It results in itchy, swollen, red, and cracked skin. The symptoms typically start in childhood with changing severity over the years. The pathogenesis of AD is characterized by excessive type 2 helper T cell mediated inflammatory responses, resulting in B lymphocyte mediated increase in serum level of immunoglobulin E (IgE). Subsequent degranulation of mast cells by IgE releases various inflammatory mediators, which recruit the lymphocytes and eosinophils into the lesion. Current clinical management of AD includes topical corticosteroids and systemic immunosuppressants. However, these drugs have been reported to carry the risk of side-effects and severe. Several recent studies including ours have demonstrated that mesenchymal stem cells (MSCs) could suppress allergic responses in AD. MSCs have been known to interact with cell types of both innate and adaptive immune systems, which results in the suppressive effect on proliferation, differentiation, and activation of immune cells including T cells, B cells, dendritic cells, and natural killer cells. Indeed, a number of studies have reported that the immunomodulatory ability of MSCs can be usefully applied for the treatment of autoimmune and inflammation-related diseases such as asthma, rhinitis, and dermatitis. Therefore, MSCs has possibility as a new drug for AD.

Official Title
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Phase I Clinical Trial to Evaluate the Safety, Tolerance, and Exploratory Efficacy of ADSTEM Inj. in Patients With Moderate to Severe, Subacute and Chronic Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: ADSTEM Inj. (Adult human mesenchymal stem cells)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Of either gender, aged ≥19 and ≤70 years Atopic dermatitis subjects who are coincident with Hanifin and Rajka diagnosis criteria Subacute and chronic atopic subjects who have atopic dermatitis symptoms continually at least 6 months Subjects with over moderate atopic dermatitis (SCORAD score > 20) Subjects who understand and voluntarily sign an informed consent form Exclusion Criteria: Subjects who have systemic infection Subjects who have human Immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) Subjects who need to take the medicine which is prohibited during this study Subjects who have asthma Subjects who can not stop treatment with topical steroids (group 1 5), oral antibiotics, whole body photochemotherapy, immunosuppressive drug within 4 weeks before the treatment visit Pregnant, breast-feeding women or women who plan to become pregnant during this study (Females of childbearing potential must have a negative urine pregnancy test) Subjects who currently participate in other clinical trial or participated in other clinical trial within 30 days Subjects who had a serious adverse events during stem cell therapy Subjects who had a hypersensitivity to antibiotics or antimycotics Subjects who creatinine value is more than two times of the upper limit of the normal range at screening test Subjects who aspartate transaminase/alkaline transaminase (AST/ALT) value is more than three times of the upper limit of the normal range at screening test Subjects who have any other condition which the investigator judges would make patients unsuitable for study participation

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intervention: Biological: ADSTEM Inj.<br>ADSTEM Inj. 1.0x10^8 mesenchymal stem cells as an intravenous infusion once for the duration of the study. ADSTEM Inj. 3.0x10^8 mesenchymal stem cells as an intravenous infusion once for the duration of the study. | Drug: ADSTEM Inj. (Adult human mesenchymal stem cells)<br>* Comparison of different dosages of the drug in the aspect of safety and efficacy.<br>* Other names: ADSTEM Inj.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects with treatment-related adverse events as assessed by CTCAE version 4.03 | physical exam, vital sign, laboratory findings, and adverse drug reactions | 12 weeks follow-up after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The reduction ratio of scoring atopic dermatitis (SCORAD) index as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of SCORAD index as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of each index score of SCORAD index as contrasted with baseline value | TBSA, erythema, edema/papulation, oozing/crusting, excoriation, lichenification, dryness, pruritus, and insomnia | 12 weeks follow-up after treatment | 
| The variation of the degrees of disease as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of investigator's global assessment (IGA) as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of eczema area and severity index (EASI) total score as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of total immunoglobulin E (IgE) in serum as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of total prostaglandin E2 (PGE2) in serum as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of total eosinophil cationic protein (ECP) in serum as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of total Chemokine ligand 17 (CCL17) in serum as contrasted with baseline value |  | 12 weeks follow-up after treatment | 
| The variation of total Chemokine ligand 27 (CCL27) in serum as contrasted with baseline value |  | 12 weeks follow-up after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic dermatitis, Mesenchymal stem cells