Safety and Efficacy of SCM-AGH in Subjects With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This study consists of two phases (Phase I and Phase II). Phase II will be conducted sequentially after the safety of SCM-AGH is secured in Phase I. Phase I: Multicenter in Korea, Randomized, Open-label, Parallel arm Phase II: Multicenter in Korea, Double-blind, Placebo-controlled, Parallel arm

Detailed Description
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Phase I (Multicenter, Randomized, Open-label, Parallel arm Design) Twenty subjects with moderate to severe Atopic Dermatitis(AD) are planned to be enrolled from 6 sites in Korea and administered with SCM-AGH by intravenous (IV) infusion 3 times at two-week intervals and evaluated for safety during the safety evaluation period (12 weeks after first infusion). Phase II (Multicenter, Double-blind, Placebo-controlled, Parallel arm) Phase II of the study is randomized, double-blind, placebo-controlled, parallel arm comparison study in adult subjects with moderate to severe AD. 72 subjects with moderate to severe AD are planned to be enrolled from 6 sites in Korea. Following up to a 4-week Screening period, subjects will be randomly assigned to one of the following treatment arms: SCM-AGH or placebo in the ratio of 1:1.

Official Title
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A Randomized, Phase I/II Trial to Evaluate the Safety and Efficacy of SCM-AGH in Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Biological: SCM-AGH
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are males or females aged >= 19 years Subjects who are diagnosed with Atopic Dermatitis (AD) based on the Eichenfield revised criteria of Hannifin and Rajka that has been present for at least 1 year before the Screening visit, and have chronic AD symptoms continually for at least 6 months before Screening visit Subjects who have moderate to severe AD (EASI ≥16) at the Screening visit and Baseline visit Subjects who have IGA score ≥3 at the Screening and Baseline visits Subjects who have at least 10% of total body surface area affected by AD at the Screening and Baseline visits Subjects who can give written informed consent Subjects must have applied a stable dose of a bland emollient to affected areas for at least 7 days before the Baseline visit and be willing to continue for the duration of the study Male subjects must abstain from heterosexual activities or agree to use a condom through 30 days after the final dose of study drug. Women of childbearing potential (WOCBP) must abstain from heterosexual activities or agree to use effective contraception through 30 days after the final dose of study drug. Effective contraception for males and/or WOCBP includes: Blockage methods - spermicides and condoms/spermicides and vaginal diaphragm for contraception, vaginal sponges or cervical cap (where available) Oral contraceptives (the pill) for at least 1 month Depot or injectable birth control or implantable contraception (e.g., Implanon) Intrauterine device (IUD) Documented evidence of surgical sterilization at least 6 months prior to Screening visit i.e., tubal ligation or hysterectomy for women or vasectomy for men Women who are post-menopausal, as documented by measurement of follicle stimulating hormone Exclusion Criteria: Systemic infection or local infection requiring prohibited medications at Screening visit Subjects who underwent the following treatments within 4 weeks prior to Baseline visit or are scheduled to receive the following treatments within 4 weeks from Baseline at the discretion of investigator: Use of immunosuppressive/ immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ (interferon-gamma), Janus kinase inhibitors, azathioprine, methotrexate) Phototherapy for AD Any other systemic therapy used to treat AD or symptoms of AD (approved or off-label use) Use of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within at least 2 weeks prior to Baseline History of anaphylaxis to any biologic therapy or vaccine History of Guillain-Barré syndrome Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained Any allergen immunotherapy within 4 months prior to or throughout the study A value outside the specified range of 90 mmHg - 140 mmHg for systolic blood pressure and 50 mmHg -90 mmHg for diastolic blood pressure (both inclusive) at Screening (can be repeated once at Screening as per Principal Investigator's [PI's] discretion). Receipt of live vaccines within 12 weeks prior to Baseline Receipt of the following biologics: Cell depleting agents such as rituximab: within 6 months prior to Baseline or within time to return of lymphocyte count to normal, whichever is longer Other biologics: within 5 half-lives or within 16 weeks prior to Baseline, whichever is longer Active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus (HCV) Female subjects who are pregnant or lactating or female subjects of childbearing potential who have a pregnancy plan or do not agree to use acceptable methods of contraception, excluding females who are in post-menopausal or surgically infertile (bilateral tubal ligation, bilateral oophorectomy or complete hysterectomy) Receipt of any investigational drugs within 8 weeks prior to baseline, within 5 half lives of investigational drug or participated in any clinical trials of medical device Diagnosed with either primary or recurrent malignancy within 5 years from Screening Liver malfunctions with aspartate aminotransferase (AST) / alanine aminotransferase (ALT) level >2x upper limit of normal (ULN) at Screening Renal malfunctions with creatinine level >2x ULN at Screening QTc (corrected QT interval) prolongation >470 msec or other significant ECG abnormality noted within 14 days of treatment History of hypersensitivity to antibiotics and antimicrobial agents History of significant Adverse Events (AEs) during stem cell therapies Allergic or hypersensitivity reaction to the IP (Investigational Product), drug of similar class or ingredients [bovine serum, dimethyl sulfoxide (DMSO)] Failure to comply with emollient application instructions prior to baseline, per diary Subjects who, in the opinion of the investigator, have other unstable intercurrent diseases that confound safety and efficacy assessment Planned or anticipated major surgical procedure during the subject's participation in this study Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedule of study procedures

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
Interventional Model Description: Phase I: Multicenter in Korea, Randomized, Open-label, Parallel arm Phase II: Multicenter in Korea, Double-blind, Placebo-controlled, Parallel arm
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCM-AGH<br>Ingredient: Allogeneic human bone marrow-derived mesenchymal stem cells Dose: 1x10^6 cells/Kg | Biological: SCM-AGH<br>* SCM-AGH will be administrated 3 times with 2-week intervals by IV infusion to subjects at Weeks 0, 2 and 4 (Visits 2, 3 and 4).<br>|
| Placebo Comparator: Placebo<br>3 times with 2-week intervals by IV infusion. | Other: Placebo<br>* Placebo will be administrated 3 times with 2-week intervals by IV infusion to subjects at Weeks 0, 2 and 4 (Visits 2, 3 and 4).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| over 50% reduction ratio of Eczema Area and Severity Index (EASI) as contrasted with baseline value (EASI-50) | An EASI score is a tool used to measure the extent (area) and severity of atopic eczema (Eczema Area and Severity Index). The minimum EASI score is 0 and the maximum EASI score is 72. Higher scores mean worse outcome. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score change from Baseline in Eczema Area and Severity Index(EASI) score | An EASI score is a tool used to measure the extent (area) and severity of atopic eczema (Eczema Area and Severity Index). The minimum EASI score is 0 and the maximum EASI score is 72. Higher scores mean worse outcome. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Percentage of subjects who have EASI-75 (improvement of ≥75% in EASI score from Baseline) | An EASI score is a tool used to measure the extent (area) and severity of atopic eczema (Eczema Area and Severity Index). The minimum EASI score is 0 and the maximum EASI score is 72. Higher scores mean worse outcome. | Weeks 12, 16, 20 and 24 | 
| Percentage of subjects who have EASI-90 (improvement of ≥90% in EASI score from Baseline) | An EASI score is a tool used to measure the extent (area) and severity of atopic eczema (Eczema Area and Severity Index). The minimum EASI score is 0 and the maximum EASI score is 72. Higher scores mean worse outcome. | Weeks 12, 16, 20 and 24 | 
| Percentage of subjects who have the Investigator's Global Assessment (IGA) score of 0 or 1 | This assessment is the overall investigator's overall global assessment for the whole body. Minimum 0 to Maximum 4. 0 means No inflammatory signs of atopic dermatitis, 4 means Marked erythema & Disease is widespread in extent. | Weeks 12, 16, 20 and 24 | 
| Percentage of subjects whose Investigator Global Assessment (IGA) score is decreased by 2 points or more | This assessment is the overall investigator's overall global assessment for the whole body. Minimum 0 to Maximum 4. 0 means No inflammatory signs of atopic dermatitis, 4 means Marked erythema & Disease is widespread in extent. | Weeks 12, 16, 20 and 24 | 
| Score change from Baseline on Pruritus Numerical Rating Scale (NRS) | The NRS is comprised of two items and represents the numbers 0 (no itch) to 10 (worst imaginable itch) in the average score of itch and the worst score of itch. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Percentage of subjects whose Pruritus Numerical Rating Scale (NRS) is improved by 3 points or more | The NRS is comprised of two items and represents the numbers 0 (no itch) to 10 (worst imaginable itch) in the average score of itch and the worst score of itch. | Weeks 12, 16, 20 and 24 | 
| Percentage change from Baseline in Body Surface Area (BSA) affected by Atopic Dermatitis (AD) | BSA involvement of AD will be assessed for each part of the body using Wallace rule of nines. This BSA is not calculated by weight and height unlike usual BSA calculation, the Wallace rule of nines is a tool used in pre-hospital and emergency medicine to estimate the total body surface area (BSA) affected by a burn. However, this study, the rule of nines will be used to measure the estimated BSA of atopic dermatitis. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Score change from Baseline in the SCORing Atopic Dermatitis (SCORAD) index | SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). Dermatologists may use this tool before and after treatment to determine whether the treatment has been effective. Maximum value is up to 103 which is the worst outcome. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Score change from Baseline in the Dermatology Life Quality Index (DLQI) | The Dermatology Life Quality Index questionnaire is designed for use in adults. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | Weeks 4, 8, 12, 16, 20 and 24 | 
| Score change from Baseline the Patient-Oriented Eczema Measure (POEM) | POEM scores are 0-2 (clear/almost clear); 3-7 (mild); 8-16 (moderate); 17-24 (severe); 25-28 (very severe) | Weeks 4, 8, 12, 16, 20 and 24 | 
| Change from Baseline in biomarker (Immunoglobulin E [IgE]) | biomarkers will be evaluated from the baseline to each time point. Unit of Measure is IU/mL. | Week 4, Week 6, Week 8, Week 12, Week 16, Week 20 and Week 24 | 
| Change from Baseline in biomarker (eosinophil count) | biomarkers will be evaluated from the baseline to each time point. Unit of measure is cells/μL. | Week 4, Week 6, Week 8, Week 12, Week 16, Week 20 and Week 24 | 
| Change from Baseline in biomarker (interleukin [IL]-13) | biomarkers will be evaluated from the baseline to each time point. Unit of measure is pg/mL. | Week 4, Week 6, Week 8, Week 12, Week 16, Week 20 and Week 24 | 
| Change from Baseline in biomarker (interleukin [IL]-17) | biomarkers will be evaluated from the baseline to each time point. Unit of measure is pg/mL. | Week 4, Week 6, Week 8, Week 12, Week 16, Week 20 and Week 24 | 
| Change from Baseline in biomarker (thymus and activation-regulated chemokine [TARC]) | biomarkers will be evaluated from the baseline to each time point. Unit of measure is pg/mL. | Week 4, Week 6, Week 8, Week 12, Week 16, Week 20 and Week 24 | 
| Change from Baseline in biomarker (interleukin [IL]-22) | biomarkers will be evaluated from the baseline to each time point. Unit of measure is pg/mL. | Week 4, Week 6, Week 8, Week 12, Week 16, Week 20 and Week 24 |