Atopic Dermatitis (AD)

Primary Objectives: Phase I: To determine the maximum tolerated dose (MTD) of AR100DP1 in healthy subjects Phase IIa: To assess the efficacy of AR100DP1 in treating atopic dermatitis Secondary Objectives: Phase I: To evaluate the safety and tolerability of AR100DP1 in healthy subjects Phase IIa: To evaluate the safety, tolerability and efficacy of AR100DP1 in subjects with mild to moderate atopic dermatitis

AR100DP1

AR100-DS1

ointment

1.25%, 2.5% and 5%

Primary Endpoints:
Phase I: Determine the MTD of AR100DP1 MTD is defined as the highest dose level at which < 2 of 6 subjects experienced a dose limiting toxicity (DLT) during Visit 2-6 (DLT observation period).
Phase IIa: Proportion of subjects with the Investigator's Static Global Assessment (ISGA) score of 0 or 1 on Day 29

Secondary Endpoints:
Phase I:
Safety:
a. Incidence of adverse events (AE) and serious adverse events (SAE) during Visit 2-6
b. Change from baseline in vital signs at Visit 2-6
c. Abnormality in physical examination at Visit 2-6
d. Transition from baseline in electrocardiogram (ECG) result at Visit 3-6
e. Change from baseline in laboratory parameters at Visit 3-6

Phase IIa:
Efficacy:
a. Proportion of subjects achieving the Investigator’s Global Static Assessment (ISGA) score of 0 (clear) or 1 (almost clear) on Day
8, Day 15, Day 22, Day 36 and Day 43
b. Change from baseline in pruritus NRS of itch level on target lesion areas on Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43
c. Change from baseline in signs of atopic dermatitis (erythema, edema, excoriation and lichenification) with grading from 0 (none) to 3 (severe) on target lesion areas on Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43
d. Percent change from baseline in Patient-Oriented Eczema Measure (POEM) total score on Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43
e. Fold change of IgE on Day 15 and Day 29 compared to baseline on Day 1 (IgED15/IgED1, IgED29/IgED1)
f. Fold change of IL-4 on Day 15 and Day 29 compared to baseline on Day 1 (IL-4D15/IL-4D1, IL-4D29/IL-4D1)
Safety:
a. Incidence of AE and SAE during Visit 2-8
b. Change from baseline in vital signs at Visit 2-8
c. Abnormality in physical examination at Visit 2-8
d. Transition from baseline in ECG result at Visit 3-8
e. Change from baseline in laboratory parameters at Visit 3-8

Phase I:
(1) Dated and signed informed consent
(2) Either gender, ≥ 20 years old (the legal age of consent majority is 20 years old in Taiwan)
(3) Healthy subjects, who have no clinically relevant abnormalities, identified by medical history, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory tests
(4) Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures
(5) Healthy skin on which reddening can be easily recognized in the area of the test fields, evaluated by the investigator
(6) Subject of childbearing potential must agree to use highly effective contraceptives from signing informed consent to 14 days after the last dose of study drug administration.
At least two forms of birth control must be adopted and one of which must be a barrier method. Acceptable forms include:
- Established use of oral, injected or implanted hormonal methods of contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom, or occlusive cap (diaphragm or cervical/vault caps)

Phase IIa:
(1) Dated and signed informed consent
(2) Either gender, ≥ 20 years old (the legal age of consent majority is 20 years old in Taiwan)
(3) Confirmed clinical diagnosis of atopic dermatitis (based on the criteria of Hanifin and Rajka for AD)
(4) Clinical diagnosis of AD that has been clinically stable, which means the ISGA score stays as 2 or 3 when evaluated for ≥ 4 weeks prior to Screening Visit
(5) With Investigator’s Static Global Assessment (ISGA) score of 2 (mild) or 3 (moderate) at screening
(6) Subject of childbearing potential must agree to use highly effective contraceptives from signing informed consent to 14 days after the last dose of study drug administration. At least two forms of birth control must be adopted and one of which must be a barrier method. Acceptable forms include:
- Established use of oral, injected or implanted hormonal methods of contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom, or occlusive cap (diaphragm or cervical/vault caps)

Phase I:
(1) Subjects who have any visible skin disease at the application site which, in the opinion of the investigator, will interfere with the evaluation of the test site reaction
(2) Subjects who have a history of AD, psoriasis and/or active AD/eczema
(3) Subjects who have damaged skin in or around the test sites, including sunburn, excessively deep tans, uneven skin tones, tattoos, scars, excessive hair, numerous freckles, or other disfigurations of the test site
(4) Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing)

Phase IIa:
(1) Unstable or actively infected AD judged by the investigator
(2) Active or potentially recurrent dermatologic condition other than atopic dermatitis that may confound evaluation, judged by the investigator
(3) Received systemic medication including corticosteroid, immunosuppressant, antihistamine, phototherapy, or other therapy, which could affect AD within 4 weeks before Screening. However, subjects are allowed to enter the study if subjects have been taking at least 2 weeks of fixed dose anti-histamine prior to Screening and this application does not affect the study judged by the investigator
(4) Received topical medication including corticosteroid, immunosuppressant, antihistamine, phototherapy, calcineurin inhibitors, or other therapy for AD on the target lesion areas within 1 week before Screening

The following exclusion criteria are applied for all subjects in Phase I/IIa study:

(1) Plan to receive immunosuppressive agents (including azathioprine, mycophenolate, cyclophosphamide, chlorambucil, methotrexate, cyclosporine), or systemic steroid with equivalent dosage higher than prednisolone 30 mg/day for more than 14 days at Screening
(2) Unwilling or unable to comply with the criteria in Life Style Guidelines during the study
(3) History of use of biologic therapy (including intravenous immunoglobulin) within 12 weeks or 5 half-lives (whichever is longer)prior to Screening
(4) Received any other investigational drug within 4 weeks prior to Screening
(5) Required or received systemic CYP3A4 inhibitors with strong potency within 1 week prior to screening, including but not limited to clarithromycin, itraconazole, nefazodone and atazanavir, evaluated by the investigator
(6) Treatment for any type of cancer (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only) within 5 years before screening
(7) Had surgery within 4 weeks prior to Screening Visit, or plan to have surgery during the study
(8) Allergies requiring acute or chronic treatment at the investigator’s discretion
(9) Known hypersensitivity to any of the components of the study drug
(10) Active clinically serious infection or history of human immunodeficiency virus (HIV) infection
(11) Any of the following serum test abnormalities:
• Total bilirubin > 1.5 × ULN
• AST or ALT > 3.0 × ULN
• Serum albumin < 2.5 g/dL
• Creatinine > 1.5 × ULN
• Any other ≥ Grade 2 (grading of vaccine clinical trials for Phase I and NCI-CTCAE v5.0 for Phase IIa) laboratory abnormality at baseline (other than those listed above)
(12) With ongoing acute diseases or within the past 2 years serious medical conditions (e.g. concomitant illness) such as cardiovascular (e.g. New York Heart Association (NYHA) grade III or IV), hepatic (e.g. Child-Pugh Class C), psychiatric condition (e.g. alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely affect the safety of the subject
(13) Female subject who is lactating or has positive urine pregnancy test at screening
(14) Other conditions not suitable for participating in this study judged by the investigator