Safety and Efficacy in Patients With Moderate to Severe Subacute and Chronic Atopic Dermatitis

Study Overview
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Brief Summary
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A Multicenter, Randomized, Single-Blind, Phase Ⅱ Clinical Trial and Open Label Long-term Observation Study of ADSTEM Inj. to Evaluate the Safety and Efficacy in Patients with Moderate to Severe Subacute and Chronic Atopic Dermatitis. The aim of this study is to evaluate the safety and efficacy of ADSTEM Inj. against Placebo in the treatment of atopic dermatitis in patients with moderate to severe acute and chronic atopic.

Detailed Description
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This clinical trial is designed with multi-organization, random assignment, single-blind, second-phase clinical trials and open long-term follow up studies, and is intended for patients with secondary or above subacuteal and chronic atopic dermatitis. If the test subjects voluntarily agree in writing to participate in this clinical trial, they shall conduct the examination and examination required for four weeks prior to administration of the investigational product (visit 1) in accordance with the clinical trial plan. As a result of the suitability assessment of the test subjects, those who comply with the inclusion/exclusion criteria, adipose tissue will be collected through the liposuction method and randomly assigned to each arms. Subjects who are eligible for administration of the investigational product on the day of administration (visit 2) under the investigator's judgment are given intravenous administration of the clinical trial medication once at the date of administration (visit 2, visit 3) and follow-up inspection is conducted at 4 weeks, 8 weeks, 12 weeks, and 16 weeks after the first administration of the investigational product and safety and efficacy assessments are conducted for a total of 16 weeks. The test subjects assigned to the placebo group shall be compensated by administering a experimental drug on demand after the visit 6. It is a principle to administer the test drug prepared from the previously obtained adipose tissue, and it is possible to carry out further adipose tissue collection if necessary. However, no safety and efficacy assessments of compensatory treatments will be collected. Safety and efficacy will be analyzed after all the subjects has completed visit 6. For the experimental group only, long-term observation study for safety assessment is conducted at the point of 6 months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months after the second administration of the investigational product for a total of 5 years.

Official Title
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A Multicenter, Randomized, Single-Blind, Phase Ⅱ Clinical Trial and Open Label Long-term Observation Study of ADSTEM Inj. to Evaluate the Safety and Efficacy in Patients With Moderate to Severe Subacute and Chronic Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: ADSTEM Inj.
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At the time of visit 1, only men and women aged between 19 and 70 Patients with atopic dermatitis meeting the Hanifin and Rajka diagnostic criteria Subacute and chronic patients with symptoms of atopic dermatitis lasting at least 6 months Patients with moderate to severe atopic dermatitis who meet all of the following criteria SCORAD score ≥ 20points EASI score ≥ 12points BSA ≥ 10% Patients with inadequate response to the stable use of topical atopic dermatitis treatment within 24 weeks prior to study initiation, or those who are unable to administer topical atopic dermatitis treatment due to safety reasons Patients who voluntarily agreed in writing to participate in this clinical trial Exclusion Criteria: Patients with systemic infection symptoms at the time of clinical trials Patients with HIV, HBV, HCV, Syphilis test positive Patients with uncontrolled asthma disease at the time of clinical trial participation Patients who were considered inevitable to receive the medication from 1 month prior to administration of the clinical trial drug to visit 6 such as Immune function modifier(tacrolimus, pimecrolimus, cyclosporine, etc.), and high-frequency topical steroids in Groups 1 to 5, systemic steroids, systemic photochemotherapy, medication that are thought to affect other immune functions (such as immunoglobulin therapy like dupilumab, tralloquinap and desensitization therapy, etc.) Women who are pregnant, breastfeeding or have a pregnancy plan up to visit 6 or who do not use available contraceptive methods (women of childbearing age must be negative in screening pregnancy test) If patients are the male subject, Those who do not agree to have a contraception during the clinical trial (If the male subject or female partner is infertile, the above-mentioned contravention method is unnecessary) Patients participating in other clinical trials or participating in other clinical trials within the last 30 days Patients who have experienced significant adverse events during treatment with stem cell therapies Patients with stem cell therapy doses or history of participating in clinical trials Patients with a history of hypersensitivity to antibiotics and antifungal agents used in the manufacture of medicines for clinical trials Patients with renal dysfunction whose creatinine level is more than twice the normal upper limit in the screening test Patients with hepatic dysfunction whose AST (Aspartate Amino Transaminase) and ALT (Alanine Amino Transaminase) levels are more than three times the normal upper limit Patients who are not suitable for this clinical trial under the judgment of the other examiners

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADSTEM Inj.<br>ADSTEM Inj. hAD-MSC 1.0x10^8 cells | Biological: ADSTEM Inj.<br>* Two 5mL of the following study drug is pre-mixed with 320mL of 0.9% normal saline is injected intravenously twice for the duration of the study. Treatment group: ADSTEM Inj. 0.5x10^8 cells/5mL<br>|
| Placebo Comparator: Placebo<br>0.9% Normal Saline Inj. | Other: Placebo<br>* 330mL of 0.9% normal saline is injected intravenously twice for the duration of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EASI-50 | Percentage of subjects whose EASI score decreased by 50% or more at 16 weeks compared to baseline | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EASI-50 | Percentage of subjects whose EASI score decreased by 50% or more at 4, 8 and 12 weeks compared to baseline | 4, 8, 12 weeks | 
| EASI-75 | Percentage of subjects whose EASI score decreased by 75% or more at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| EASI score | EASI score change at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| SCORAD-50 | Percentage of subjects whose SCORAD score decreased by 50% or more at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| SCORAD-75 | Percentage of subjects whose SCORAD score decreased 75% or more at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| SCORAD score | SCORAD score change at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| SCORAD subgroup | SCORAD evaluation items(Extent Criteria, erythema, edema/population, oozing/crusting, excoriation, lichenification, dryness, pruritus, insomnia) score change at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| Severity | Severity change of disease at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| IGA grade | Investigator's Global Assessment (IGA) score at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| IGA -1 or more grade | Percentage of subjects who dropped one or more grades on the Investigator's Global Assessment (IGA) score at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| IGA -2 or more grade | Percentage of subjects who dropped two or more grades on the Investigator's Global Assessment (IGA) score at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| Total IgE | Total IgE change at 4, 8, 12, 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| PGE2 and ECP | Prostaglandin E2 (PGE2) and Eosinophil Cationic Protein (ECP) changes at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| Immune cytokine | TGF-1, interleukin (IL)-4, 5, 6, 8, 13, 31 and CCL17 at 4, 8, 12 and 16 weeks compared to baseline | 4, 8, 12, 16 weeks | 
| Remedy used days and frequency | Days and frequency of used remedies at 4, 8, 12 and 16 weeks | 4, 8, 12, 16 weeks | 
| Remedy used subjects | Percentage of subjects whom used remedies at 4, 8,12 and 16 weeks | 4, 8, 12, 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adipose Derived Mesenchymal Stem cell, ADMSC, AD, Inflammatory disease, ADMC, Stem cell, ehlbio