Atopic Dermatitis
Conditions
Keywords
Moderate-to-severe atopic dermatitis, Etrasimod, APD334
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).
Interventions
DRUGEtrasimod 1 mg
Etrasimod 1 mg tablet taken by mouth, once daily
DRUGEtrasimod 2 mg
Etrasimod 2 mg tablet taken by mouth, once daily.
DRUGEtrasimod matching placebo
Etrasimod matching placebo tablet by mouth, once daily.
Sponsors
Arena Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Treatment Period: Percent Change in Eczema Area and Severity Index (EASI) Score | Baseline (Day 1) and Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (Day 1) and Week 12 | 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. |
| Double-blind Treatment Period: Percent Change in Weekly Peak Pruritus Numerical Rating Scale (NRS) From an Itch Daily Diary | Baseline (Day 1) and Week 12 | 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. |
| 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 | Baseline (Day 1) and Week 12 | 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. |
| Double-blind Treatment Period: Percentage of Participants Achieving EASI-50 | Baseline (Day 1) and Week 12 | 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. |
| Double-blind Treatment Period: Percentage of Participants Achieving EASI-90 | Baseline (Day 1) and Week 12 | 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. |
| Double-blind Treatment Period: Percent Change in Percent Body Surface Area (BSA) | Baseline (Day 1) and Week 12 | 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 |
| Open-label Extension (OLE) Period: Percent Change in EASI | Baseline (Week 16) and Week 68 | 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. |
| Double-blind Treatment Period: Percentage of Participants Achieving EASI-75 | Baseline (Day 1) and Week 12 | 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. |
| OLE Period: Number of Participants Achieving a Validated Investigator Global Assessment (vIGA) 0 or 1 Score and a Reduction From Baseline of ≥ 2 Points | Baseline (Week 16) and Week 68 | 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. |
| OLE Period: Percent Change in SCORing Atopic Dermatitis (SCORAD) Total Score | Baseline (Week 16) and Week 68 | 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. |
| OLE Period: Percent Change in Percent BSA | Baseline (Week 16) and Week 68 | 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. |
| OLE Period: Percent Change in Weekly Peak Pruritus NRS From an Itch Daily Diary | Baseline (Week 16) and Week 28 | 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. |
| OLE Period: Change in Patient-Oriented Eczema Measure (POEM) | Baseline (Week 16) and Week 68 | 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. |
| OLE Period: Change in Dermatology Life Quality Index (DLQI) | Baseline (Week 16) and Week 68 | 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. |
| OLE Period: Change in Patient Global Assessment (PGA) of Disease | Baseline (Week 16) and Week 68 | 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. |
| OLE Period: Number of Participants Achieving a EASI-75 Score | Baseline (Week 16) and Week 68 | 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. |
Countries
Australia, Canada, United States
Participant flow
Recruitment details
This was a 2-treatment period study (12-Week Double-Blind Treatment Period and 52-Week Open-label extension \[OLE\] Period), to evaluate the safety and efficacy of etrasimod monotherapy compared with placebo in participants with moderate-to-severe atopic dermatitis (AD), whose disease was not adequately controlled with topical therapies.
Pre-assignment details
A total of 140 participants were randomized into the 12-week Double-Blind Treatment Period and a total of 95 participants continued into the 52-Week OLE Period.
Participants by arm
| Arm | Count |
|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) Participants with chronic AD were randomized to receive etrasimod 1 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study. | 47 |
| Double-blind Treatment Period: Etrasimod 2 mg Participants with chronic AD were randomized to receive etrasimod 2 mg orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study. | 47 |
| Double-blind Treatment Period: Placebo Participants with chronic AD were randomized to receive placebo orally once daily for 12 weeks. Participants who successfully completed 12 weeks of Double-blind treatment continued to have access to etrasimod in the OLE period of the study. | 46 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Treatment (12-Week) | Adverse Event | 2 | 5 | 0 | 0 |
| Double-blind Treatment (12-Week) | Lost to Follow-up | 5 | 1 | 6 | 0 |
| Double-blind Treatment (12-Week) | Other | 0 | 1 | 1 | 0 |
| Double-blind Treatment (12-Week) | Physician Decision | 1 | 0 | 0 | 0 |
| Double-blind Treatment (12-Week) | Protocol deviation | 1 | 1 | 0 | 0 |
| Double-blind Treatment (12-Week) | Withdrawal by Subject | 4 | 3 | 2 | 0 |
| OLE Period (52-Week) | Adverse Event | 0 | 0 | 0 | 5 |
| OLE Period (52-Week) | Lost to Follow-up | 0 | 0 | 0 | 9 |
| OLE Period (52-Week) | Physician Decision | 0 | 0 | 0 | 1 |
| OLE Period (52-Week) | Protocol deviation | 0 | 0 | 0 | 2 |
| OLE Period (52-Week) | Withdrawal by Subject | 0 | 0 | 0 | 10 |
Baseline characteristics
| Characteristic | Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Double-blind Treatment Period: Etrasimod 2 mg | Double-blind Treatment Period: Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 41.7 Years STANDARD_DEVIATION 13.32 | 41.8 Years STANDARD_DEVIATION 14.83 | 44.1 Years STANDARD_DEVIATION 16.16 | 42.5 Years STANDARD_DEVIATION 14.74 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 18 Participants | 11 Participants | 44 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 27 Participants | 26 Participants | 31 Participants | 84 Participants |
| Sex: Female, Male Female | 30 Participants | 28 Participants | 27 Participants | 85 Participants |
| Sex: Female, Male Male | 17 Participants | 19 Participants | 19 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 47 | 0 / 46 | 0 / 95 |
| other Total, other adverse events | 19 / 47 | 31 / 47 | 22 / 46 | 53 / 95 |
| serious Total, serious adverse events | 0 / 47 | 0 / 47 | 0 / 46 | 3 / 95 |
Outcome results
Primary
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.
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Double-blind Treatment Period: Percent Change in Eczema Area and Severity Index (EASI) Score | -58.68 Percent change | Standard Error 7.735 |
| Double-blind Treatment Period: Etrasimod 2 mg | Double-blind Treatment Period: Percent Change in Eczema Area and Severity Index (EASI) Score | -57.18 Percent change | Standard Error 7.8 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change in Eczema Area and Severity Index (EASI) Score | -48.41 Percent change | Standard Error 8.378 |
Comparison: Week 12p-value: =0.119895% CI: [-23.228, 2.674]ANCOVA
Comparison: Week 12p-value: =0.178395% CI: [-21.544, 4.002]ANCOVA
Secondary
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.
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | 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 | 14.9 Percentage of participants |
| Double-blind Treatment Period: Etrasimod 2 mg | 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 | 29.8 Percentage of participants |
| Double-blind Treatment Period: Placebo | 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 | 13.0 Percentage of participants |
Comparison: Week 12p-value: =0.769495% CI: [-12.29, 16.64]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: =0.04595% CI: [0.79, 34]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Double-blind Treatment Period: Percentage of Participants Achieving EASI-50 | 61.7 Percentage of participants |
| Double-blind Treatment Period: Etrasimod 2 mg | Double-blind Treatment Period: Percentage of Participants Achieving EASI-50 | 66.0 Percentage of participants |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percentage of Participants Achieving EASI-50 | 52.2 Percentage of participants |
Comparison: Week 12p-value: =0.398195% CI: [-11.27, 28.8]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: =0.14195% CI: [-4.72, 35.15]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Double-blind Treatment Period: Percentage of Participants Achieving EASI-75 | 27.7 Percentage of participants |
| Double-blind Treatment Period: Etrasimod 2 mg | Double-blind Treatment Period: Percentage of Participants Achieving EASI-75 | 38.3 Percentage of participants |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percentage of Participants Achieving EASI-75 | 26.1 Percentage of participants |
Comparison: Week 12p-value: =0.982695% CI: [-18.52, 18.11]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: =0.189195% CI: [-6.12, 32.21]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Double-blind Treatment Period: Percentage of Participants Achieving EASI-90 | 19.1 Percentage of participants |
| Double-blind Treatment Period: Etrasimod 2 mg | Double-blind Treatment Period: Percentage of Participants Achieving EASI-90 | 14.9 Percentage of participants |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percentage of Participants Achieving EASI-90 | 10.9 Percentage of participants |
Comparison: Week 12p-value: =0.26995% CI: [-6.61, 23.38]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: =0.542895% CI: [-9.56, 18.25]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | 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 | 45.0 Percentage of participants |
| Double-blind Treatment Period: Etrasimod 2 mg | 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 | 45.0 Percentage of participants |
| Double-blind Treatment Period: Placebo | 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 | 41.0 Percentage of participants |
Comparison: Week 12p-value: =0.714395% CI: [-18, 26.41]Cochran-Mantel-Haenszel
Comparison: Week 12p-value: =0.648895% CI: [-16.62, 26.87]Cochran-Mantel-Haenszel
Secondary
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
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Double-blind Treatment Period: Percent Change in Percent Body Surface Area (BSA) | -34.725 Percent change | Standard Error 7.047 |
| Double-blind Treatment Period: Etrasimod 2 mg | Double-blind Treatment Period: Percent Change in Percent Body Surface Area (BSA) | -45.153 Percent change | Standard Error 6.86 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change in Percent Body Surface Area (BSA) | -31.913 Percent change | Standard Error 7.012 |
Comparison: Week 12p-value: =0.716395% CI: [-18.089, 12.466]Mixed Models Analysis
Comparison: Week 12p-value: =0.08495% CI: [-28.284, 1.805]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (Day 1) and Week 12
Population: Full Analysis Set Population. Only those participants with data available at the specified time points were analyzed
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Double-blind Treatment Period: Percent Change in Weekly Peak Pruritus Numerical Rating Scale (NRS) From an Itch Daily Diary | -38.401 Percent change | Standard Error 8.236 |
| Double-blind Treatment Period: Etrasimod 2 mg | Double-blind Treatment Period: Percent Change in Weekly Peak Pruritus Numerical Rating Scale (NRS) From an Itch Daily Diary | -35.044 Percent change | Standard Error 7.91 |
| Double-blind Treatment Period: Placebo | Double-blind Treatment Period: Percent Change in Weekly Peak Pruritus Numerical Rating Scale (NRS) From an Itch Daily Diary | -24.374 Percent change | Standard Error 8.492 |
Comparison: Week 12p-value: =0.055895% CI: [-28.406, 0.352]Mixed Models Analysis
Comparison: Week 12p-value: =0.136395% CI: [-24.737, 3.397]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Change in Dermatology Life Quality Index (DLQI) | -5.4 Scores on a scale | Standard Deviation 6.03 |
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Change in Patient Global Assessment (PGA) of Disease | 1.23 Scores on a scale | Standard Deviation 1.209 |
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Change in Patient-Oriented Eczema Measure (POEM) | -6.3 Scores on a scale | Standard Deviation 6.5 |
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Number of Participants Achieving a EASI-75 Score | 65 Participants |
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Number of Participants Achieving a Validated Investigator Global Assessment (vIGA) 0 or 1 Score and a Reduction From Baseline of ≥ 2 Points | 31 Participants |
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Percent Change in Percent BSA | -68.47 Percent change | Standard Deviation 52.083 |
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Percent Change in SCORing Atopic Dermatitis (SCORAD) Total Score | -64.27 Percent change | Standard Deviation 69.273 |
Secondary
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.
Time frame: Baseline (Week 16) and Week 28
Population: Safety Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | OLE Period: Percent Change in Weekly Peak Pruritus NRS From an Itch Daily Diary | -36.87 Percent change | Standard Deviation 45.219 |
Secondary
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.
Time frame: Baseline (Week 16) and Week 68
Population: Safety Set Population included all randomized participants who received at least 1 dose of study intervention. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Treatment Period: Etrasimod 1 Milligrams (mg) | Open-label Extension (OLE) Period: Percent Change in EASI | -45.39 Percent change | Standard Deviation 258.796 |