Atopic Dermatitis
Conditions
Keywords
Atopic dermatitis, Eczema, AD, AQX-1125, SHIP1
Brief summary
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
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.
Interventions
DRUGAQX-1125
Synthetic SHIP1 activator
DRUGPlacebo
Sponsors
Innovaderm Research Inc.
Aquinox Pharmaceuticals (Canada) Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Lesion Symptom Score (TLSS) | 12 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Investigator's Global Assessment (IGA) | 12 weeks | 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). |
| Change From Baseline in Eczema Area and Severity Index (EASI) Score | 12 weeks | 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. |
| Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | 12 weeks | 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). |
| Change From Baseline in Patient Oriented Eczema Measure (POEM) Score | 12 weeks | 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AQX-1125 1 x AQX-1125 Capsule daily
AQX-1125: Synthetic SHIP1 activator | 26 |
| Placebo 1 x placebo capsule daily
Placebo | 28 |
| Total | 54 |
Baseline characteristics
| Characteristic | AQX-1125 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 28 Participants | 54 Participants |
| BMI | 26.4 kg/m2 STANDARD_DEVIATION 6.17 | 27.1 kg/m2 STANDARD_DEVIATION 5.28 | 26.8 kg/m2 STANDARD_DEVIATION 5.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 28 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 25 Participants | 44 Participants |
| Region of Enrollment Canada | 26 participants | 28 participants | 54 participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 32 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 22 Participants |
| Weight | 72.96 kg STANDARD_DEVIATION 19.44 | 76.30 kg STANDARD_DEVIATION 16.06 | 74.69 kg STANDARD_DEVIATION 17.67 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 28 |
| other Total, other adverse events | 17 / 26 | 14 / 28 |
| serious Total, serious adverse events | 0 / 26 | 0 / 28 |
Outcome results
Primary
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
Time frame: 12 weeks
Population: The intent to treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in Total Lesion Symptom Score (TLSS) | Baseline | 6.3 units on a scale | Standard Deviation 1.16 |
| AQX-1125 | Change From Baseline in Total Lesion Symptom Score (TLSS) | Week 12 (Change from baseline) | -1.9 units on a scale | Standard Deviation 2.19 |
| Placebo | Change From Baseline in Total Lesion Symptom Score (TLSS) | Baseline | 6.6 units on a scale | Standard Deviation 1.31 |
| Placebo | Change From Baseline in Total Lesion Symptom Score (TLSS) | Week 12 (Change from baseline) | -1.9 units on a scale | Standard Deviation 2.41 |
Comparison: A sample size of 20 subjects per group was assumed to have 80% power to allow detection of a statistically significant difference in change from baseline in TLSS between the 2 groups, if the effect size was approximately less than or equal to 0.9. This is equivalent to detecting a difference of -4.5 between the 2 groups with a common standard deviation of 5. The primary analysis was doing using last observation carried forward (LOCF) imputed data.p-value: 0.63695% CI: [-1.3, 1.25]ANCOVA
Secondary
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.
Time frame: 12 weeks
Population: The intent to treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline | 5.58 units on a scale | Standard Deviation 3.34 |
| AQX-1125 | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Week 12 (Change from baseline) | -2.84 units on a scale | Standard Deviation 1.55 |
| Placebo | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline | 5.35 units on a scale | Standard Deviation 2.24 |
| Placebo | Change From Baseline in Eczema Area and Severity Index (EASI) Score | Week 12 (Change from baseline) | -2.12 units on a scale | Standard Deviation 3.19 |
p-value: 0.80295% CI: [-1.983, 1.544]ANOVA
Secondary
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).
Time frame: 12 weeks
Population: The intent to treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in Investigator's Global Assessment (IGA) | Baseline | 2.6 units on a scale | Standard Deviation 0.5 |
| AQX-1125 | Change From Baseline in Investigator's Global Assessment (IGA) | Week 12 (Change from baseline) | -0.7 units on a scale | Standard Deviation 0.98 |
| Placebo | Change From Baseline in Investigator's Global Assessment (IGA) | Baseline | 2.8 units on a scale | Standard Deviation 0.52 |
| Placebo | Change From Baseline in Investigator's Global Assessment (IGA) | Week 12 (Change from baseline) | -0.8 units on a scale | Standard Deviation 0.87 |
p-value: 0.67795% CI: [-0.44, 0.68]ANOVA
Secondary
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.
Time frame: 12 weeks
Population: The intent to treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in Patient Oriented Eczema Measure (POEM) Score | Baseline | 16.7 units on a scale | Standard Deviation 6.98 |
| AQX-1125 | Change From Baseline in Patient Oriented Eczema Measure (POEM) Score | Week 12 (Change from baseline) | -5.6 units on a scale | Standard Deviation 9.7 |
| Placebo | Change From Baseline in Patient Oriented Eczema Measure (POEM) Score | Baseline | 15.9 units on a scale | Standard Deviation 5.48 |
| Placebo | Change From Baseline in Patient Oriented Eczema Measure (POEM) Score | Week 12 (Change from baseline) | -6.5 units on a scale | Standard Deviation 5.82 |
p-value: 0.23395% CI: [-1.68, 6.72]ANOVA
Secondary
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).
Time frame: 12 weeks
Population: The intent to treat analysis population (ITT) is the set of subjects who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AQX-1125 | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | Baseline | 36.19 units on a scale | Standard Deviation 8.7 |
| AQX-1125 | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | Week 12 (Change from baseline) | -12.06 units on a scale | Standard Deviation 11.15 |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | Baseline | 37.21 units on a scale | Standard Deviation 6.38 |
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | Week 12 (Change from baseline) | -11.54 units on a scale | Standard Deviation 11.49 |
p-value: 0.97695% CI: [-7.076, 7.292]ANOVA