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

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

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

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: AQX-1125

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • AQX-Innovaderm site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged from 18 to 65 years old
2. Confirmed clinical diagnosis of active atopic dermatitis (AD) according to the Hanifin and Rajka criteria
3. At least a 6 months history of atopic dermatitis.
4. Body Surface Area (BSA) covered with atopic dermatitis of 1% or more
5. Mild or moderate atopic dermatitis (IGA score of 2 or 3).
6. TLSS of 5 or more at Day 0.
7. 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:

1. Female subject who is pregnant or breast-feeding
2. Unstable or clinically infected atopic dermatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AQX-1125; 1 x AQX-1125 Capsule daily	Drug: AQX-1125; Synthetic SHIP1 activator
Placebo Comparator: Placebo; 1 x placebo capsule daily	Drug: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aquinox Pharmaceuticals (Canada) Inc.
• Collaborators: Innovaderm Research Inc.
• Investigators: Study Director: Maggie Wang, MD, Aquinox Pharamceuticals Inc

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: December 23, 2014
• First Posted (Estimate): December 24, 2014

Study Record Updates

• Last Update Posted (Actual): October 5, 2018
• Last Update Submitted That Met QC Criteria: December 8, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Atopic dermatitis; AD; Eczema; AQX-1125; SHIP1
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: AQX-1125-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO