Safety and Efficacy of FURESTEM-AD Inj. for Moderate to Severe Atopic Dermatitis (AD)

Study Overview
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Brief Summary
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This clinical trial study is two-stage, multi-center, randomized, double-blind, placebo controlled, phase 3 clinical trial to evaluate the efficacy and safety of FURESTEM-AD Inj. for moderate to severe chronic atopic dermatitis.

Official Title
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A Two-stage, Multi-center, Randomized, Double-Blind, Placebo Controlled, Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of FURESTEM-AD Inj. for Moderate to Severe Chronic Atopic Dermatitis

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Biological: FURESTEM-AD® inj. 5.0 X 10^7 cells/1.5 mL
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 19 years and older at time of informed consent Subjects diagnosed with atopic dermatitis based on the Hanifin and Rajka diagnostic criteria Subjects with chronic atopic dermatitis that has been present for at least 1 year before screening Subjects with moderate to severe atopic dermatitis as indicated by: EASI score ≥ 16 points at the time of screening and baseline (Day 1), IGA score ≥ 3 points at the time of screening and baseline (Day 1), and BSA affected by atopic dermatitis ≥ 10% at the time of screening and baseline (Day 1) Subjects who have documented history of insufficient response to stable use of atopic dermatitis treatment within 24 weeks before screening, or inability to receive such treatment because of safety issues Subjects who are willing to apply a stable dose of non-medicated topical moisturizer at least twice daily for at least 7 days before the baseline (Day 1) visit and the duration of the study Women of childbearing potential who use appropriate contraceptive methods during this trial period Subjects who have voluntarily agreed to participate in this trial in writing Exclusion Criteria: Subjects with the following history of disease or surgery/procedure at screening Malignancy or lympho-proliferative disease within 5 years before screening (except completely treated carcinoma in situ of the cervix, or completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin) organ transplants History of mental illness, drug or alcohol abuse within 2 years before screening, as per Investigator's opinion Subjects with the following underlying disease at screening Chronic active, acute infection or superficial skin infections requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals or antifungals; Skin diseases, pigmentation, or extensive scarring other than atopic dermatitis that may affect the efficacy evaluations of the study Renal dysfunction with serum creatinine level > 2.0 mg/dL at screening Liver dysfunction with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2.5 times the upper limit of the normal range (ULN) at the time of screening Subjects with the history of using leukotriene receptor antagonists, systemic steroids, phototherapy, systemic immunosuppressants/modulators including janus kinase (JAK) inhibitors, and/or any other systemic therapy (not mentioned in Exclusion Criteria 6 and 8) to treat atopic dermatitis or symptoms of atopic dermatitis (approved or off-label use) within 4 weeks before baseline (Day 1) Subjects with the history of using systemic or topical antihistamines, topical corticosteroids (TCS), topical calcineurin inhibitors (TCIs), or topical phosphodiesterase 4 (PDE4) inhibitors within 2 weeks before baseline (Day 1) Allergen immunotherapy within 6 months before baseline (Day 1) Subjects with the history of receipt of the following treatments before baseline (Day 1) B cell-depleting agents including rituximab within 6 months Other biologics including dupilumab within 5 half-lives (if known) or 12 weeks, whichever is longer Subjects with regular use (more than two times per a week) of a tanning booth/parlor within 4 weeks before screening visit Subjects with the history of a live (attenuated) vaccine injection within 12 weeks before baseline (Day 1) or the plan to inject a live (attenuated) vaccine within 24 weeks after randomization Subjects who are deemed to require prohibited concomitant medications drug/therapy during the study period Subjects with uncontrolled chronic disease that might require administration of oral corticosteroids such as uncontrolled and severe asthma Pregnant/lactating women and men and women of childbearing potential who plan to become pregnant or who refuse to use appropriate contraceptive methods during the study period Subjects with the history of receipt of any investigational products or devices from another clinical trial within 4 weeks or 5 half-lives (if known) pior to screening Positive serology for hepatitis B or C, or for HIV Subjects with prior use of FURESTEM-AD Subjects with history of anaphylaxis Subjects who are deemed to have difficulty in performing this study by the judgment of the Investigator and those with other medical findings that are unsuitable for participation in the study

Ages Eligible for Study
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Minimum Age: 19 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Furestem-AD Inj.<br>Investigational product name: FURESTEM-AD® inj. 5.0 X 10^7 cells/1.5 mL baseline (0week) Experimental group will receive Investigational product (FURESTEM-AD® inj. 5.0 X 10^7 cells/1.5 mL). After 12 weeks, Experimental group will receive placebo. | Biological: FURESTEM-AD® inj. 5.0 X 10^7 cells/1.5 mL<br>* the following study drug is injected respectively into both upper arms, both thighs, and abdomen (total of 5 regions)<br>Biological: Placebo<br>* the following study drug is injected respectively into both upper arms, both thighs, and abdomen (total of 5 regions)<br>|
| Placebo Comparator: Placebo<br>Placebo baseline (0week) Placebo comparator group will receive placebo. After 12 weeks, Placebo comparator group will receive Investigational product (FURESTEM-AD® inj. 5.0 X 10^7 cells/1.5 mL). | Biological: FURESTEM-AD® inj. 5.0 X 10^7 cells/1.5 mL<br>* the following study drug is injected respectively into both upper arms, both thighs, and abdomen (total of 5 regions)<br>Biological: Placebo<br>* the following study drug is injected respectively into both upper arms, both thighs, and abdomen (total of 5 regions)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EASI(Eczema Area and Severity Index)-50 | Ratio of subject whose Eczema Area and Severity Index (EASI) decreased over 50% as contrasted with baseline value | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EASI(Eczema Area and Severity Index)-75 | Ratio of subjects whose Eczema Area and Severity Index (EASI) decreased over 75% as contrasted with baseline value | 2,4,8,12 weeks | 
| EASI(Eczema Area and Severity Index)-50 | Ratio of subjects whose Eczema Area and Severity Index (EASI) decreased over 50% as contrasted with baseline value | 2,4,8 weeks | 
| EASI(Eczema Area and Severity Index) index | Change and rate of change in Eczema Area and Severity Index (EASI) index as contrasted with baseline value | 2,4,8,12 weeks | 
| IGA(Investigator's Global Assessment) Score | Proportion of subjects who Investigator's Global Assessment (IGA) score 0 or 1 and at least 2 points reduction in IGA score as contrasted with baseline value | 2,4,8,12 weeks | 
| SCORAD(SCORing Atopic Dermatitis)-50 | Ratio of subjects whose SCORing Atopic Dermatitis (SCORAD) decreased over 50% as contrasted with baseline value | 2,4,8,12 weeks | 
| SCORAD(SCORing Atopic Dermatitis) index | Change and rate of change in SCORing Atopic Dermatitis (SCORAD) index as contrasted with baseline value | 2,4,8,12 weeks | 
| BSA(Body Surface Area) | Change and rate of change in Body Surface Area (BSA) as contrasted with baseline value | 2,4,8,12 weeks | 
| Worst daily Pruritus NRS(Numerical Rating Scale) | Rate of change in Worst daily Pruritus Numerical Rating Scale (NRS) as contrasted with baseline value | 2,4,8,12 weeks | 
| Average daily Pruritus NRS(Numerical Rating Scale) | Rate of change in Average daily Pruritus Numerical Rating Scale (NRS) as contrasted with baseline value | 2,4,8,12 weeks | 
| Worst daily Pruritus NRS(Numerical Rating Scale) - 4 points | Proportion of patients at least 4 points reduction in Worst daily Pruritus Numerical Rating Scale (NRS) as contrasted with baseline value | 2,4,8,12 weeks | 
| POEM(Patient-Oriented Eczema Measure) | Change and rate of change in Patient-Oriented Eczema Measure (POEM) as contrasted with baseline value | 2,4,8,12 weeks | 
| DLQI(Dermatology Life Quality Index) | Change and rate of change in Dermatology Life Quality Index (DLQI) as contrasted with baseline value | 2,4,8,12 weeks | 
| Rescue medicine | Total number of use and consumed amount of rescue medicine | up to 12, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, AD, Stem cell, Furestem