Pilot Efficacy and Safety Study of AQX-1125 in Atopic Dermatitis

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effect of 12 weeks of treatment with once daily administration of AQX-1125 compared to placebo on change from baseline in Total Lesion Symptom Score in subjects with mild to moderate atopic dermatitis

Detailed Description
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One of the causative factors for the inflammatory response observed in AD is the release of chemokines and other chemoattractant factors followed by recruitment of inflammatory cell subtypes (10). IL-16, a Langerhans cells (LC)-derived chemoattractant cytokine for CD4+ cells, RANTES, monocyte chemotactic protein (MCP-4) and eotaxin are overexpressed in epidermal keratinocytes from AD subjects and may contribute to the chemotaxis of eosinophils, macrophages and Th2-lymphocytes (11). Since the activation of SHIP1 by AQX-1125 results in the inhibition of inflammatory cell chemotaxis and reduction of pro-inflammatory cytokine synthesis, this study hypothesized that AQX-1125 would improve AD.

Official Title
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The KINSHIP Trial: A Randomized, Double-Blind, Multicenter, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of AQX-1125 in Subjects With Atopic Dermatitis by Targeting the SHIP1 Pathway

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: AQX-1125
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged from 18 to 65 years old Confirmed clinical diagnosis of active atopic dermatitis (AD) according to the Hanifin and Rajka criteria At least a 6 months history of atopic dermatitis. Body Surface Area (BSA) covered with atopic dermatitis of 1% or more Mild or moderate atopic dermatitis (IGA score of 2 or 3). TLSS of 5 or more at Day 0. Subject must use a non-medicated emollient daily for at least (≥) 7 days prior to Day 0 and should continue using that same emollient, at the same frequency, throughout the study. Exclusion Criteria: Female subject who is pregnant or breast-feeding Unstable or clinically infected atopic dermatitis

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: AQX-1125<br>1 x AQX-1125 Capsule daily | Drug: AQX-1125<br>* Synthetic SHIP1 activator<br>|
| Placebo Comparator: Placebo<br>1 x placebo capsule daily | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Lesion Symptom Score (TLSS) | The TLSS is an assessment of the severity of each of the following three signs: erythema, papulation/infiltration, excoriation and lichenification. Each of these items are rated using a 4-point scale severity where 0 is clear, 1 = mild, 2= moderate and 3 = severe. These ratings are then added to create a total score ranging from 0 to 12 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Investigator's Global Assessment (IGA) | The IGA is a global assessment of the current state of the disease. It is a 5-point morphological assessment of overall disease severity and will be determined according to the following categories: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (severe). | 12 weeks | 
| Change From Baseline in Eczema Area and Severity Index (EASI) Score | The Eczema Area and Severity Index (EASI) quantifies the severity of a subject's atopic dermatitis based on both lesion severity and the percentage of body surface area (BSA) affected. Lesions are assessed on four domains; 1) erythema, 2) induration/papulation, 3) excoriation and 4) lichenification. Each domain is scored separately over four body regions (head/neck, upper limbs, trunk and lower limbs) on a scale of 0-3 (0 = none, 1 = mild, 2 = moderate and 3 = severe) with adjustment for the percentage of BSA involved for each body region and for the proportion of the body region relative to the whole body. The sum of these scores provides the EASI total score, ranging from 0 to 72 with a higher score indicating greater severity of atopic dermatitis. | 12 weeks | 
| Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | The severity scoring of atopic dermatitis (SCORAD) index is a standard tool to assess the atopic dermatitis (AD) severity in clinical studies. Six items; erythema, edema/papulation, oozing/crusts, excoriation, lichenification and dryness are measured on a scale from 0-3 for a total of 18 points, with a higher score indicating greater severity. The percentage of BSA affected by AD is evaluated (percentage divided by 5) and added to the total SCORAD score. Loss of sleep and pruritus are also evaluated by subjects on a visual analog scale (scores ranging from 0-10) with a higher score indicating greater severity. The sum of these measures represents the SCORAD which ranges from 0 (absent disease) to 103 (severe disease). | 12 weeks | 
| Change From Baseline in Patient Oriented Eczema Measure (POEM) Score | The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic dermatitis, Eczema, AD, AQX-1125, SHIP1