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

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

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

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Etrasimod 1 mg; Drug: Etrasimod 2 mg; Drug: Etrasimod matching placebo

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Premier Specialists Pty Ltd
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Sinclair Dermatology
• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Recherche Sherbrooke Inc.
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Noble Clinical Research
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology
    • Huntington Beach, California, United States, 92647
      • Marvel Research LLC
    • Inglewood, California, United States, 90301
      • ADVA Clinical Research, Inc
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • San Diego, California, United States, 92123
      • TCR Medical Corporation
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Doral, Florida, United States, 33166
      • Prohealth Research Center
    • Hialeah, Florida, United States, 33016
      • Aby's New Generation Research, Inc.
    • Hollywood, Florida, United States, 33021
      • Skin Care Research, Llc
    • Homestead, Florida, United States, 33030
      • Advanced Research Institute of Miami LLC
    • Homestead, Florida, United States, 33030
      • Amber Pediatrics Research, LLC
    • Miami, Florida, United States, 33155
      • South Miami Medical & Research Group. Inc
    • Miami, Florida, United States, 33169
      • Amber Pediatrics Research, LLC
    • Miami, Florida, United States, 33173
      • Skin Research of South Florida
    • Miami Shores, Florida, United States, 33138
      • Amber Clinical Research, LLC
    • Saint Petersburg, Florida, United States, 33709
      • IMA Clinical Research, LLC
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
  • Georgia
    • Union City, Georgia, United States, 30291
      • Rophe Adult and Pediatric Medicine/SKYCRNG
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Skin Sciences Pllc
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • Quinn Healthcare/SKYCRNG
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research Inc
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
  • New York
    • New York, New York, United States, 10012
      • Greenwich Village Dermatology
  • Oregon
    • Portland, Oregon, United States, 97210
      • ODRC Enterprises, LLC dba Oregon Dermatology and Research Center
  • South Carolina
    • Spartanburg, South Carolina, United States, 29369
      • Spartanburg Medical Research
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Texas
    • Beaumont, Texas, United States, 77702
      • Gadolin Research
    • Dallas, Texas, United States, 75231
      • Modern Research Associates, PLLC
    • Georgetown, Texas, United States, 78626
      • FMC Science
    • Lampasas, Texas, United States, 76550
      • FMC Science
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Alliance for Multispecialty Research
    • Richmond, Virginia, United States, 23220
      • Clinical Research Partners, LLC
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Arena Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2019
• Primary Completion (Actual): September 9, 2020
• Study Completion (Actual): October 11, 2021

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Etrasimod; APD334; Moderate-to-severe atopic dermatitis
• 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: APD334-201

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No