A Study to Assess the Safety and Efficacy of ZPL389 in Patients With Moderate to Severe 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 to assess safety and efficacy of ZPL389 in subjects with moderate to severe atopic dermatitis with a total study duration up to 24 weeks

Detailed Description
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A screening period of up to 4 weeks was followed by a 16-week double blinded treatment period. After the end of treatment visit, subjects were offered the possibility of ongoing treatment in the extension study (CZPL389A2203E1/ NCT03948334), or of entering the 4 week treatment-free follow-up period.

Official Title
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A Randomized, Double-blind, Placebo-controlled Multicenter Dose Ranging Study to Assess the Safety and Efficacy of Multiple Oral ZPL389 Doses in Patients With Moderate to Severe Atopic Dermatitis (ZEST Trial)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Placebo
* Drug: ZPL389 3mg
* Drug: ZPL389 10mg
* Drug: ZPL389 30mg
* Drug: ZPL389 50mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must give a written, signed and dated informed consent Chronic atopic dermatitis present for at least 1 year before Baseline Moderate to severe atopic dermatitis defined as per EASI, IGA and BSA. Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable Candidate for systemic treatment Exclusion Criteria: Any skin disease that would confound the diagnosis or evaluation of atopic dermatitis disease activity Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer. History of hypersensitivity to any of the study drug constituents or to drugs of similar chemical classes. Participation in prior ZPL389 studies

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Placebo Comparator: placebo<br>Placebo | Drug: Placebo<br>* once daily from baseline until week 16<br>|
| Experimental: ZPL389 3mg<br>ZPL389 3 mg oral powder | Drug: ZPL389 3mg<br>* ZPL389 3 mg oral powder; once daily from baseline to week 16<br>|
| Experimental: ZPL389 10 mg<br>ZPL389 10 mg oral powder | Drug: ZPL389 10mg<br>* ZPL389 10 mg oral powder; once daily from baseline to week 16<br>|
| Experimental: ZPL389 30mg<br>ZPL389 30 mg oral powder | Drug: ZPL389 30mg<br>* ZPL389 30 mg oral powder; once daily from baseline to week 16<br>|
| Experimental: ZPL389 50mg<br>ZPL389 50 mg oral powder | Drug: ZPL389 50mg<br>* ZPL389 50 mg oral powder; once daily from baseline to week 16<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of IGA Responders at Week 16 | Investigator's Global Assessment (IGA) score is used to determine the severity of atopic dermatitis symptoms and clinical response to treatment. It reflects a subject's overall disease severity for the whole body. The scale includes 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. It is a static scale and does not refer to previous status of the subject. IGA response is defined as achievement of an IGA score of 0 or 1 with a 2-point reduction from baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline IGA as covariates. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in EASI Score at Week 16 | Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema. | Baseline, Week 16 | 
| Percent Change From Baseline in EASI Score Over Time | Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema. | Baseline, Week 2, Week 4, Week 6, Week 8, Week 12 | 
| Percentage of EASI50 Responders Over Time | Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema. EASI50 response is defined as achieving ≥ 50% improvement (reduction) in EASI score compared to baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline EASI as covariates | Week 2, Week 4, Week 6, Week 8, Week 12, Week 16 | 
| Percentage of EASI75 Responders Over Time | Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema. EASI75 response is defined as achieving ≥ 75% improvement (reduction) in EASI score compared to baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline EASI as covariates | Week 2, Week 4, Week 6, Week 8, Week 12, Week 16 | 
| Percentage of IGA Responders Over Time | Investigator's Global Assessment (IGA) score is used to determine the severity of atopic dermatitis symptoms and clinical response to treatment. It reflects a subject's overall disease severity for the whole body. The scale includes 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. It is a static scale and does not refer to previous status of the subject. IGA response is defined as achievement of an IGA score of 0 or 1 with a 2-point reduction from baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline IGA as covariates. | Week 2, Week 4, Week 6, Week 8, Week 12 | 
| Number of Patients With Adverse Events | An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study until the end of study visit. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. | Up to week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atopic dermatitis, AD, eczema, atopic eczema, itch, pruritus, histamine 4 receptor, antagonist, H4R, ZPL389, ZPL389A2203, dermatitis