Study of ATI-1777 in Patients 12 to 65 Years Old With Mild to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This is a Phase 2b study to determine the safety, tolerability, pharmacokinetic (PK), and efficacy of ATI-1777 in patients 12 to 65 years old with mild to severe Atopic Dermatitis. Eligible participants will apply either ATI-1777 or Vehicle Topical Solution once daily or twice daily for 4 weeks.

Official Title
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A Phase 2b, Multicenter, Randomized, Double-Blind, Vehicle-Controlled, Parallel-Group Study to Determine the Safety, Tolerability, Pharmacokinetics, and Efficacy of ATI-1777 in Patients 12 to 65 Years Old With Mild to Severe Atopic Dermatitis (AD)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: ATI-1777 2.0% w/w
* Drug: ATI-1777 1.0% w/w
* Drug: ATI-1777 0.5% w/w
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to comprehend and willing to sign the IRB approved ICF/assent prior to administration of study-related procedures. Male patients or non-pregnant, non-nursing female patients 12 to 65 years old, inclusive, at the time of informed consent/assent. 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. 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. Female patients who are pregnant, nursing, or planning to become pregnant during the study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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: Randomized, Double-blind, Vehicle-controlled, Parallel-group Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATI-1777 topical solution 2.0% w/w (BID)<br>ATI-1777 topical solution 2.0% w/w, twice daily | Drug: ATI-1777 2.0% w/w<br>* ATI-1777 topical solution 2.0% w/w<br>|
| Experimental: ATI-1777 topical solution 1.0% w/w (BID)<br>ATI-1777 topical solution 1.0% w/w, twice daily | Drug: ATI-1777 1.0% w/w<br>* ATI-1777 topical solution 1.0% w/w<br>|
| Experimental: ATI-1777 topical solution 0.5% w/w (BID)<br>ATI-1777 topical solution 0.5% w/w, twice daily | Drug: ATI-1777 0.5% w/w<br>* ATI-1777 topical solution 0.5% w/w<br>|
| Placebo Comparator: Vehicle (BID)<br>Vehicle topical solution, twice daily | Drug: Vehicle<br>* Vehicle topical solution<br>|
| Experimental: ATI-1777 topical solution 2.0% w/w (QD)<br>ATI-1777 topical solution 2.0% w/w, once daily | Drug: ATI-1777 2.0% w/w<br>* ATI-1777 topical solution 2.0% w/w<br>|
| Placebo Comparator: Vehicle (QD)<br>Vehicle topical solution, once daily | Drug: Vehicle<br>* Vehicle topical solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in Eczema Area and Severity Index Score (EASI) score at Week 4 (Day 28) | EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in EASI score at each post-baseline study visit |  | Baseline to Day 42 | 
| Proportion achieving Investigator's Global Assessment-Treatment Success (IGA-TS) defined as Validated Investigator Global Assessment (vIGA) score of 0 or 1 with an improvement in vIGA of at least 2 points from baseline at each post-baseline study visit. | IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). An IGA responder was defined as a participant achieving an IGA score of 0 to 1 and an IGA score improvement at least 2 from baseline. | Baseline to Day 42 | 
| Proportion of patients who achieve 50%, 75%, and 90% improvement in EASI score (EASI 50, EASI 75, and EASI 90, respectively) at each post-baseline study visit |  | Baseline to Day 42 | 
| Change from baseline in vIGA score at each post-baseline study visit |  | Baseline to Day 42 | 
| Change from baseline in Body Surface Area (BSA) at each post-baseline study visit | BSA is defined as a percentage of the total body (0-100) that is affected by disease | Baseline to Day 42 | 
| Number of Participants With At Least One Adverse Event (AEs) and as Per Severity | AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. The severity of AEs was assessed using CTCAE v4.03 Grades 1 through 4.Data are reported for Grade 3 and higher severity for this outcome measure. | Baseline to Day 42 | 
| Change from baseline in Itch Numerical Rating Scale (PP NRS) from baseline to Day 28 | The Itch NRS is a once-per-24 hours (daily) participant-reported measure of itch intensity to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. The categorical NRS is defined as 0 = None, 1 to 3 = Mild, 4 to 6 = Moderate, and 7 to 10 = Severe.study visit | Baseline to Day 28 |