A Phase 2a, Multicenter, Randomized, Double-blind, Vehicle-controlled, Parallel-group Study to Determine the Safety, Tolerability, Pharmacokinetics and Efficacy of ATI-1777 in Adult Patients With Moderate or Severe Atopic Dermatitis
Overview
- Phase
- Phase 2
- Intervention
- ATI-1777
- Conditions
- Atopic Dermatitis
- Sponsor
- Aclaris Therapeutics, Inc.
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 4
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a first-in-human, randomized, double-blind, parallel-group, vehicle-controlled study to evaluate the efficacy, safety, tolerability, and PK of ATI-1777 solution following twice-daily applications to target areas of participants with moderate or severe atopic dermatitis (AD).
Detailed Description
Participants underwent screening evaluations to determine eligibility up to 30 days prior to randomization. Participants who meet all the entry criteria were randomized on Day 1 to active or vehicle treatment. Participants applied study drug (ATI-1777 topical solution 2.0% w/w or vehicle) twice daily for 4 weeks with weekly study visits and were to return 2 weeks after the last dose of study medication for a Post treatment Follow-up (PTFU) Visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to comprehend and willing to sign the IRB approved informed consent form (ICF) prior to administration of study-related procedures.
- •Male patients or non-pregnant, non-nursing female patients 18 to 65 years old, inclusive, at the time of informed consent.
- •Pregnancy and Contraception:
- •Women of childbearing potential (WOCBP), must have a negative serum pregnancy test at the Screening Visit, a negative urine pregnancy test immediately prior to the first application of study medication on Day 1, and a negative urine pregnancy test at each study visit thereafter.
- •WOCBP must agree to use 2 forms of highly effective contraception, including 1 physical barrier (condom or diaphragm) plus another highly effective method, such as adequate hormonal method (e.g., contraceptive implants, injectables, oral contraceptives) or nonhormonal methods (e.g., intrauterine device, spermicidals) throughout the Screening Period and until 30 days after the last administration of study medication.
- •Male patients with partners of childbearing potential may be enrolled if they are:
- •Documented to be surgically sterile (vasectomy), or
- •Using 2 adequate forms of highly effective contraception, 1 of which should be a physical barrier until 90 days after the last administration of study medication.
- •Have a diagnosis of AD fulfilling the specified diagnostic criteria of Hanifin and Rajka (Hanifin and Rajka 1980).
- •Have at least a 6-month history of AD prior to the Screening Visit, and no significant AD flares for the 4 weeks prior to the Screening Visit.
Exclusion Criteria
- •Unstable course of AD (spontaneously improving or rapidly deteriorating) based on the patient history or as determined by the investigator during the Screening Period.
- •Refractory AD (i.e., AD that required frequent hospitalizations and/or frequent intravenous treatment for skin infections within the year before the Screening Visit).
- •AD of a severity (EASI \>48) that the patient is not a candidate for a vehicle-controlled study.
- •Any signs or symptoms associated with AD therapy (e.g., history of anaphylaxis, hypersensitivity reactions, skin atrophy, striae, pigmentary changes) that, in the investigator's opinion, might impair evaluation of the AD or which exposes the patient to unacceptable risk by study participation.
- •Concomitant skin disease or clinically infected AD or presence of other skin disease in the area to be dosed that may interfere with study assessments.
- •Use of any of the following treatments within the indicated washout period prior to Day 1:
- •Phototherapy (ultraviolet A, ultraviolet B, or psoralen and ultraviolet A therapy) within 4 weeks prior to Day
- •Systemic biologic immunosuppressant or immunomodulatory therapy (e.g., etanercept, alefacept, infliximab, dupilumab) within 12 weeks (or 5 half-lives of the product, whichever is longer) prior to Day
- •Non-biologic immunosuppressants (e.g., methotrexate, retinoids, calcineurin inhibitors, cyclosporine, hydroxycarbamide \[hydroxyurea\], azathioprine) within 4 weeks prior to Day
- •Janus kinase (JAK) inhibitors (systemic and topical) within 4 weeks prior to Day
Arms & Interventions
ATI-1777
ATI-1777 topical solution 2.0% w/w, twice daily
Intervention: ATI-1777
Vehicle
Vehicle topical solution, twice daily
Intervention: Vehicle
Outcomes
Primary Outcomes
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 4
Time Frame: Baseline, Week 4
The EASI evaluation was performed by the Principal Investigator and evaluated atopic dermatitis in each of 3 body regions (trunk \[excluding groin and genitalia\], upper extremities \[excluding palms of hands\], and lower extremities \[excluding soles of feet\]). The EASI scoring system uses a defined process to grade the severity of the signs of atopic dermatitis and the extent affected. EASI Scores ranged from 0-72, with higher scores indicative of more severe disease.
Secondary Outcomes
- Number of Participants Who Achieve 75% Improvement in EASI Score (EASI-75) by Week 4(Week 4)
- Change From Baseline in Percent of Body Surface Area (BSA) of Atopic Dermatitis at Days 8 and 15 and Week 4(Baseline, Days 8 and 15, and Week 4)
- Percent Change From Baseline in EASI Score at Days 8 and 15(Baseline, Days 8 and 15)
- Number of Participants Who Achieve 50% Improvement in EASI Score (EASI 50) by Week 4(Week 4)
- Number of Participants Who Achieve 90% Improvement in EASI Score (EASI-90) by Week 4(Week 4)
- Change From Baseline in Investigator Global Assessment (IGA) Score for Atopic Dermatitis at Days 8 and 15, and Week 4(Baseline, Days 8 and 15, and Week 4)
- Change From Baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) Score at Days 8 and 15, and Week 4(Baseline, Days 8 and 15, and Week 4)