A Study to Assess the Safety and Efficacy of Etrasimod in Subjects With Moderate-to-Severe Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether etrasimod is a safe and effective treatment for moderate-to-severe atopic dermatitis (AD).

Official Title
-----------------
A Multicenter, Randomized, Double-Blinded, Placebo-Controlled 16-Week Study (With a 52-Week Open-Label Extension) to Assess the Safety and Efficacy of Etrasimod in Subjects With Moderate-to-Severe Atopic Dermatitis

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: Etrasimod 1 mg
* Drug: Etrasimod 2 mg
* Drug: Etrasimod matching placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Participants with chronic atopic dermatitis, defined by Hanifin and Rajka criteria, that has been present for at least 1 year prior to the Screening Visit Participants with Eczema Area and Severity Index (EASI) ≥ 12 at the Screening Visit and ≥ 16 at the Baseline Visit Participants with validated Investigator's Global Assessment (vIGA) score ≥ 3 (on the 0 to 4 vIGA scale, in which 3 = moderate and 4 = severe) involvement at the Screening and Baseline visits Exclusion Criteria: Presence of skin comorbidities that would interfere with study assessments of the underlying disease.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12-Week Double-Blind Treatment Period: Etrasimod 1 milligrams (mg)<br> | Drug: Etrasimod 1 mg<br>* Etrasimod 1 mg tablet taken by mouth, once daily<br>* Other names: APD334;|
| Experimental: 12-Week Double-Blind Treatment Period: Etrasimod 2 mg<br> | Drug: Etrasimod 2 mg<br>* Etrasimod 2 mg tablet taken by mouth, once daily.<br>* Other names: APD334;|
| Placebo Comparator: 12-Week Double-Blind Treatment Period: Placebo<br> | Drug: Etrasimod matching placebo<br>* Etrasimod matching placebo tablet by mouth, once daily.<br>|
| Experimental: 52-Week Open-Label Extension Period: Etrasimod 2 mg<br> | Drug: Etrasimod 2 mg<br>* Etrasimod 2 mg tablet taken by mouth, once daily.<br>* Other names: APD334;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double-blind Treatment Period: Percent Change in Eczema Area and Severity Index (EASI) Score | EASI evaluates severity of participant's AD based on severity of AD clinical signs and percent (%) of body surface area (BSA) affected. EASI is a composite scoring assessment of the affected area in 4 specific disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification), which was each assessed on a scale of 0 (absent) through 3 (severe). The EASI Area Score is documented for 4 regions of the body. Region 1: head and neck; Region 2: trunk (including genital area); Region 3: upper limbs; and Region 4: lower limbs (including buttocks), with the area of AD involvement assessed as a percentage by body area and converted to a score of 0 to 6. Total EASI score ranged from 0 to 72; higher score indicated greater severity of AD. Baseline is defined as Day 1 pre-randomization assessments. | Baseline (Day 1) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double-blind Treatment Period: Percentage of Participants Achieving EASI-75 | EASI-75 is defined as a 75% reduction or greater in EASI score from Baseline to Week 12. Baseline is defined as Day 1 pre-randomization assessments. | Baseline (Day 1) and Week 12 | 
| Double-blind Treatment Period: Percentage of Participants Achieving a Validated Investigator Global Assessment (vIGA) 0 or 1 Score and a Reduction From Baseline of >= 2 Points | The vIGA scale for AD is a 5-point scale to measure disease severity. The vIGA score was selected using descriptors that best described the overall appearance of skin lesions at a given time point using the following scoring: 0 = clear (no inflammatory signs of AD); 1 = almost clear (barely perceptible erythema and papulation); 2 = mild (slight but definite erythema and papulation); 3 = moderate (clearly perceptible erythema and papulation); and 4 = severe (marked erythema and papulation); Higher score indicated greater severity. Baseline is defined as Day 1 pre-randomization assessments. | Baseline (Day 1) and Week 12 | 
| Double-blind Treatment Period: Percent Change in Weekly Peak Pruritus Numerical Rating Scale (NRS) From an Itch Daily Diary | Pruritus NRS is an assessment tool that was used to report the intensity of a participant's pruritus (itch). The scale for the pruritus NRS ranged from 0 to 10 with 0 being no itch and 10 being the worst itch imaginable; higher scores indicated greater severity. Baseline is defined as Day 1 pre-randomization assessments. | Baseline (Day 1) and Week 12 | 
| Double-blind Treatment Period: Percentage of Participants With Improvement (Reduction) in Peak Pruritus NRS Greater Than or Equal to (>=)3 From an Itch Daily Diary | Pruritus NRS is an assessment tool that was used to report the intensity of a participant's pruritus (itch). The scale for the pruritus NRS ranged from 0 to 10 with 0 being no itch and 10 being the worst itch imaginable; higher scores indicated greater severity. Percentage of participants with improvement (reduction) in peak pruritus NRS >=3 from an itch daily diary is presented. Baseline is defined as Day 1 pre-randomization assessments. | Baseline (Day 1) and Week 12 | 
| Double-blind Treatment Period: Percentage of Participants Achieving EASI-50 | EASI-50 is defined as a 50% reduction or greater of EASI from Baseline to Week 12. Percentage of participants achieving EASI-50 is presented. Baseline is defined as Day 1 pre-randomization assessments. | Baseline (Day 1) and Week 12 | 
| Double-blind Treatment Period: Percentage of Participants Achieving EASI-90 | EASI-90 is defined as as a 90% reduction or greater of EASI from Baseline to Week 12. Percentage of participants achieving EASI-90 is presented Baseline is defined as Day 1 pre-randomization assessments. | Baseline (Day 1) and Week 12 | 
| Double-blind Treatment Period: Percent Change in Percent Body Surface Area (BSA) | BSA affected by AD were assessed for each section of the body. The possible highest score for each region was: head and neck (9%), anterior trunk (18%), back (18%), upper limbs (18%), lower limbs (36%), and genitals (1%) and were reported as a percentage of all major body sections combined; higher % BSA indicated greater severity. Baseline is defined as Day 1 pre-randomization assessments | Baseline (Day 1) and Week 12 | 
| Open-label Extension (OLE) Period: Percent Change in EASI | EASI evaluates severity of participant's AD based on severity of AD clinical signs and percent (%) of body surface area (BSA) affected. EASI is a composite scoring assessment of the affected area in 4 specific disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification), which was each assessed on a scale of 0 (absent) through 3 (severe). The EASI Area Score is documented for 4 regions of the body. Region 1: head and neck; Region 2: trunk (including genital area); Region 3: upper limbs; and Region 4: lower limbs (including buttocks), with the area of AD involvement assessed as a percentage by body area and converted to a score of 0 to 6. Total EASI score ranged from 0 to 72; higher score indicated greater severity of AD. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16. | Baseline (Week 16) and Week 68 | 
| OLE Period: Number of Participants Achieving a EASI-75 Score | EASI evaluates severity of participant's AD based on severity of AD clinical signs and percent (%) of body surface area (BSA) affected. EASI is a composite scoring assessment of the affected area in 4 specific disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification), which was each assessed on a scale of 0 (absent) through 3 (severe). The EASI Area Score is documented for 4 regions of the body. Region 1: head and neck; Region 2: trunk (including genital area); Region 3: upper limbs; and Region 4: lower limbs (including buttocks), with the area of AD involvement assessed as a percentage by body area and converted to a score of 0 to 6. Total EASI score ranged from 0 to 72; higher score indicated greater severity of AD. EASI-75 is defined as a >=75% reduction or greater of EASI from Baseline. | Baseline (Week 16) and Week 68 | 
| OLE Period: Number of Participants Achieving a Validated Investigator Global Assessment (vIGA) 0 or 1 Score and a Reduction From Baseline of ≥ 2 Points | The vIGA scale for AD is a 5-point scale to measure disease severity. The vIGA score was selected using descriptors that best described the overall appearance of skin lesions at a given time point using the following scoring: 0 = clear (no inflammatory signs of AD); 1 = almost clear (barely perceptible erythema and papulation); 2 = mild (slight but definite erythema and papulation); 3 = moderate (clearly perceptible erythema and papulation); and 4 = severe (marked erythema and papulation); Higher score indicated greater severity. | Baseline (Week 16) and Week 68 | 
| OLE Period: Percent Change in SCORing Atopic Dermatitis (SCORAD) Total Score | The SCORAD is a validated measure of the extent and severity of AD using 3 components: A = extent or affected BSA, B = severity and C = subjective symptoms. The extent of AD was assessed as percentage of each defined body area and reported as the sum of all areas, with a maximum score of 100%. The severity of 6 specific symptoms was assessed using the following scale: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points, assigned as B in the overall SCORAD calculation). Subjective assessment of itch and sleeplessness was recorded for each symptom by the participant or relative on a Visual Analogue Scale, where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum possible score of 20. This parameter is assigned as C in the overall SCORAD calculation. The total SCORAD ranged from 0 (no disease) to 103 (severe disease); higher score indicated more severe AD. | Baseline (Week 16) and Week 68 | 
| OLE Period: Percent Change in Percent BSA | BSA affected by AD were assessed for each section of the body. The possible highest score for each region was: head and neck (9%), anterior trunk (18%), back (18%), upper limbs (18%), lower limbs (36%), and genitals (1%) and were reported as a percentage of all major body sections combined; higher % BSA indicated greater severity. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16. | Baseline (Week 16) and Week 68 | 
| OLE Period: Percent Change in Weekly Peak Pruritus NRS From an Itch Daily Diary | Pruritus NRS is an assessment tool that was used to report the intensity of a participant's pruritus (itch). The scale for the pruritus NRS ranged from 0 to 10 with 0 being no itch and 10 being the worst itch imaginable; higher scores indicated greater severity. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16. | Baseline (Week 16) and Week 28 | 
| OLE Period: Change in Patient-Oriented Eczema Measure (POEM) | The POEM is a participant-derived validated tool used for monitoring atopic eczema severity. The POEM consisted of 7 questions asking participants to rank how many days over the past 7 days they had experienced specific AD-related symptoms. Each of the 7 questions carried equal weight and was scored from 0 to 4 as follows: No days = 0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; Every day = 4. The scores from the 7 questions were added up to give an overall POEM score as: 0-2 = 'clear/almost clear', 3-7 = 'mild', 8-16 = 'moderate', 17-24 = 'severe', and 25-28 = 'very severe atopic eczema'; higher scores indicated worse atopic eczema severity. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16. | Baseline (Week 16) and Week 68 | 
| OLE Period: Change in Dermatology Life Quality Index (DLQI) | The DLQI is a validated 10-item questionnaire designed to measure the impact of skin disease on the Quality of Life (QoL). DLQI is a response to 10 items, which assessed QoL over the past week. For each item, the scale was rated as follows: 0 = not at all; 1 = a little; 2 = a lot; 3 = very much, with an overall scoring system of 0 to 30; higher scores indicated a poor QoL. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16. | Baseline (Week 16) and Week 68 | 
| OLE Period: Change in Patient Global Assessment (PGA) of Disease | PGA is an assessment tool that was used by participant to rate the disease and disease severity. Participants rated their overall well-being based on a 5-point Likert scale from poor to excellent. Response choices were: 1- 'Poor', 2- 'Fair', 3- 'Good', 4- 'Very Good,' or 5- 'Excellent'; higher scores indicated better well-being. For the 5-point Likert scale, a positive change from baseline indicates an improvement. Baseline is defined as the last measurement prior to the first etrasimod dose started at Week 16. | Baseline (Week 16) and Week 68 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
APD334, Moderate-to-severe atopic dermatitis, Etrasimod