A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Atopic Dermatitis

Study Overview
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Brief Summary
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This was a randomized, double blind, placebo controlled, parallel group study in approximately 90 subjects with moderate-severe AD Eczema Area and Severity Index (EASI) ≥12 and ≤ 48 (0-72 scale). Following a run-in subjects were randomized to receive either oral 30 mg ZPL-3893787 once daily (od) or placebo od for 8 weeks (56 days).

Official Title
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A Randomized, Double-blind, Placebo Controlled, Parallel Group Study to Determine the Effects of 8 Weeks Treatment With Oral ZPL-3893787 (30 mg od x 56 Days) on Pruritus in Adult Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: ZPL-3893787
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-65 years inclusive with physician documented history or diagnosis of atopic dermatitis for at least 12 months prior to screening. Chronic AD should be diagnosed by the Eichenfield revised criteria of Hanifin and Rajka (Eichenfield, 2004) Eczema Area and Severity Index (EASI) of ≥12 and <48. An Investigator's Global Assessment (IGA) score ≥ 3 at both Screening and Day 0. A mean pruritus score of ≥ 5 on a 0-10 scale over the 7 day Run In (Days -7 to -1) Atopic dermatitis affecting ≥10% BSA Exclusion Criteria: AD of such severity (EASI >48) that the subject could not comply with the demands of the study and/or the subject is not a suitable candidate for a placebo-controlled study Have concurrent skin disease (e.g. acne) of such severity in the study area that it could interfere with the study evaluation or presence of skin comorbidities that may interfere with study assessments. Have an active skin infection or any other clinically apparent infections. Hypersensitivity to mometasone or to any other ingredients contained by the topical corticosteroid product used as rescue medication in the study. Have received phototherapy (e.g. UVA, UVB), or systemic therapy (e.g. immunosuppressants, cytostatics) known or suspected to have an effect on AD, within 4 weeks of the start of the Run In. Have received systemic corticosteroids ([CS] e.g. oral, intravenous, intraarticular, rectal) within 4 weeks of the start of the Run in. Subjects on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal CS may participate. Were treated with oral antihistamines or topical calcineurin inhibitors or topical steroids within 7 days of starting Run In; intranasal antihistamines for the treatment of allergic rhinitis are acceptable.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZPL-3893787<br>30 mg ZPL-3893787 orally once daily for 8 weeks. | Drug: ZPL-3893787<br>* ZPL-3893787<br>|
| Placebo Comparator: Placebo<br>1 capsule orally once daily for 8 weeks. | Drug: Placebo<br>* Matched Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | The participant used the Pruritus NRS to rate his or her worst itch in the previous 12 hours. This was assessed twice daily (in the morning soon after rising and the evening prior to retiring) and recorded in the eDiary. The scale ranges from 0 (no itching) to 10 (itching as bad as can be imagined). If only 1 measurement was collected on a particular day, that score was counted as the worst measurement. | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Eczema Area and Severity Index (EASI) Score | The EASI is a validated tool used to measure the severity and extent of atopic eczema over 4 body regions (head and neck, upper limbs, trunk, and lower limbs). The intensity of a representative area of eczema and the approximate percentage affected by eczema are calculated for each region. A representative area of eczema is selected for each body region. The intensity of redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) of eczema is assessed as: 0 - None - Mild - Moderate - Severe The total score incorporates the extent of body regions affected. Scores range from 0 to 72 with higher scores indicating more severe eczema. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions | Baseline to Week 8 |