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

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

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

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.

Inclusion Criteria:

1. Subjects who are males or females aged >= 19 years

2. Subjects who are diagnosed with Atopic Dermatitis (AD) based on the Eichenfield revised criteria of Hannifin and Rajka that

   1. has been present for at least 1 year before the Screening visit, and
   2. have chronic AD symptoms continually for at least 6 months before Screening visit

3. Subjects who have moderate to severe AD (EASI ≥16) at the Screening visit and Baseline visit

4. Subjects who have IGA score ≥3 at the Screening and Baseline visits

5. Subjects who have at least 10% of total body surface area affected by AD at the Screening and Baseline visits

6. Subjects who can give written informed consent

7. 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

8. 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:

1. Systemic infection or local infection requiring prohibited medications at Screening visit

2. 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:

   1. Use of immunosuppressive/ immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ (interferon-gamma), Janus kinase inhibitors, azathioprine, methotrexate)
   2. Phototherapy for AD
   3. Any other systemic therapy used to treat AD or symptoms of AD (approved or off-label use)

3. Use of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within at least 2 weeks prior to Baseline

4. History of anaphylaxis to any biologic therapy or vaccine

5. History of Guillain-Barré syndrome

6. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained

7. Any allergen immunotherapy within 4 months prior to or throughout the study

8. 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).

9. Receipt of live vaccines within 12 weeks prior to Baseline

10. Receipt of the following biologics:

    1. 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
    2. Other biologics: within 5 half-lives or within 16 weeks prior to Baseline, whichever is longer

11. Active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus (HCV)

12. 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)

13. 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

14. Diagnosed with either primary or recurrent malignancy within 5 years from Screening

15. Liver malfunctions with aspartate aminotransferase (AST) / alanine aminotransferase (ALT) level >2x upper limit of normal (ULN) at Screening

16. Renal malfunctions with creatinine level >2x ULN at Screening

17. QTc (corrected QT interval) prolongation >470 msec or other significant ECG abnormality noted within 14 days of treatment

18. History of hypersensitivity to antibiotics and antimicrobial agents

19. History of significant Adverse Events (AEs) during stem cell therapies

20. Allergic or hypersensitivity reaction to the IP (Investigational Product), drug of similar class or ingredients [bovine serum, dimethyl sulfoxide (DMSO)]

21. Failure to comply with emollient application instructions prior to baseline, per diary

22. Subjects who, in the opinion of the investigator, have other unstable intercurrent diseases that confound safety and efficacy assessment

23. Planned or anticipated major surgical procedure during the subject's participation in this study

24. Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedule of study procedures