A Study for AR100DP1 in Mild to Moderate Atopic Dermatitis (AD)

NCT04220411 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AR100DP1-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/IIa Open-Label, Dose-Escalation Study to Determine the Safety, Tolerability, and Efficacy of AR100DP1 in Health Subjects, and Subjects with Mild to Moderate Atopic Dermatitis.

Conditions

Dermatitis, Atopic

Outcome Measures

Primary Outcomes (3)

• Number of Subjects With DLTs

  Phase I study included 14 days of treatment with AR100DP1, followed by 2 weeks of follow-up period to find the maximum tolerated dose (MTD) of AR100DP1. DLTs were defined as any adverse event (AE) ≥ Grade 2 (Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, issued by United States Food and Drug Administration in September 2007), that was considered to be causally related (possibly, probably, or definitely related) to AR100DP1 as judged by the investigator up to Day 29. The definition of Grade 5 (death related to AE) was added to this grading system as it was not defined in the guidance. (reported in the subsequent Primary Outcome Measure). MTD is defined as the highest dose level at which \< 2 of 6 subjects experienced a dose-limiting toxicity (DLT).

  up to Day 29 for each cohort in phase I

• Maximum Tolerated Dose (MTD) of AR100DP1

  Per protocol, MTD is defined as the highest dose level at which \< 2 of 6 subjects experienced a dose-limiting toxicity (DLT). MTD was determined by testing increasing doses up to 125 mg/day via topical administration on AR100DP1\_1.25%, 2.5%, and 5% groups with 3 to 6 subjects each. DLTs were defined as any adverse event (AE) ≥ Grade 2 (Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, issued by United States Food and Drug Administration in September 2007), that was considered to be causally related (possibly, probably, or definitely related) to AR100DP1 as judged by the investigator up to Day 29. The definition of Grade 5 (death related to AE) was added to this grading system as it was not defined in the guidance. (reported in the previous Primary Outcome Measure).

  up to Day 29 for each cohort in phase I

• Percentage of Subjects With the Investigator's Global Assessment (IGA) Score of 0 or 1 on Day 29 (Phase IIa)

  The IGA is a 5-point scale that provides a global clinical assessment of AD severity based on an ordinal scale, scored by the investigator. The scores of IGA are 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (Severe).

  Day 29 (Phase IIa)

Secondary Outcomes (18)

• Percentage of Subjects With the Investigator's Global Assessment (IGA) Score of 0 ~ 4 (Phase IIa)

  Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (Phase IIa)

• Change From Baseline in Pruritus Numerical Rating Scale (NRS) of Itch Level on Target Lesions

  Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (Phase IIa)

• Change of IgE Compared to Baseline (Day 1)

  Day 15 and 29 (Phase IIa)

• Fold Change of IL-4 Compared to Baseline (Day 1 )

  Day 15 and 29 (Phase IIa)

• Change From Baseline in Signs of Atopic Dermatitis (Erythema, Edema, Excoriation and Lichenification) on Target Lesions

  Day 8, Day 15, Day 22, Day 29, Day 36 and Day 43 (Phase IIa)

Study Arms (4)

AR100DP1 (1.25%)_Phase I

EXPERIMENTAL

Subjects topically apply AR100DP1 twice per day with at least 4 hour interval. The daily dosage of 1.25% AR100DP1 topical administration is 31.25 mg/day (1.25% × 1,250 × 2 = 31.25).

Drug: AR100DP1

AR100DP1 (2.5%)_Phase I

EXPERIMENTAL

Subjects topically apply AR100DP1 twice per day with at least 4 hour interval. The daily dosage of 2.5% AR100DP1 topical administration is 62.5 mg/day (2.5% × 1,250 × 2 = 62.5).

Drug: AR100DP1

AR100DP1 (5%)_Phase I

EXPERIMENTAL

Subjects topically apply AR100DP1 twice per day with at least 4 hour interval. The daily dosage of 5% AR100DP1 topical administration is 125 mg/day (5% × 1,250 × 2 = 125).

Drug: AR100DP1

AR100DP1 (5%)_Phase IIa

EXPERIMENTAL

Subjects topically apply AR100DP1 twice per day with at least 4 hour interval. The daily dosage of 5% AR100DP1 topical administration is 125 mg/day (5% × 1,250 × 2 = 125).

Drug: AR100DP1

Interventions

AR100DP1 DRUG

topical ointment

AR100DP1 (1.25%)_Phase I; AR100DP1 (2.5%)_Phase I; AR100DP1 (5%)_Phase I; AR100DP1 (5%)_Phase IIa

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase I:
• Dated and signed informed consent
• Either gender, ≥ 20 years old (the legal age of consent majority is 20 years old in Taiwan)
• Healthy subjects, who have no clinically relevant abnormalities, identified by medical history, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures
• Healthy skin on which reddening can be easily recognized in the area of the test fields, evaluated by the investigator
• Subject of childbearing potential must agree to use abstinence to intercourse, or highly effective contraceptives from signing informed consent to 14 days after the last dose of study drug administration
• At least two forms of effective birth control must be adopted for contraception, 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 (highly recommended with spermicide), or occlusive cap (diaphragm or cervical/vault caps)
• Phase IIa:
• Dated and signed informed consent
• Either gender, ≥ 20 years old (the legal age of consent majority is 20 years old in Taiwan)
• Confirmed clinical diagnosis of atopic dermatitis (based on the criteria of Hanifin and Rajka for AD)

You may not qualify if:

• Phase I:
• 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
• Subjects who have a history of AD, psoriasis and/or active AD/eczema
• 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
• 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:
• Unstable or actively infected AD judged by the investigator.
• Active or potentially recurrent dermatologic condition other than atopic dermatitis that may confound evaluation (e.g. fungal infection), judged by the investigator.
• Received systemic medication including corticosteroid, immunosuppressant, anti-histamine, 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
• Received topical medication including corticosteroid, immunosuppressant, anti-histamine, phototherapy, calcineurin inhibitors, or other therapy for AD on the target lesion area(s) within 1 week before Screening
• 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
• Unwilling or unable to comply with the criteria in Life Style Guidelines during the study
• History of use of biologic therapy (including intravenous immunoglobulin) within 12 weeks or 5 half-lives (whichever is longer) prior to Screening
• Received any other investigational drug within 4 weeks prior to Screening
• 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

Sponsors & Collaborators

• Arjil Pharmaceuticals LLC: lead

Study Sites (1)

Arjil Pharmaceuticals LLC.

Hsinchu, Taiwan

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: YEH B, WU
• Organization: Arjil Pharmaceuticals LLC.

ybw333@arjilbio.com

+886-3-573-3608

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I: conventional 3+3 design of dose escalation Phase IIa: single-arm

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 7, 2020
• Study Start: December 8, 2020
• Primary Completion: December 29, 2021
• Study Completion: June 13, 2022
• Last Updated: December 11, 2023
• Results First Posted: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)