Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether oral etrasimod is a safe and effective treatment for moderately to severely active ulcerative colitis.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Assess the Efficacy and Safety of Etrasimod in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Etrasimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosed with ulcerative colitis (UC) ≥ 3 months prior to screening Active UC confirmed by endoscopy Exclusion criteria: Severe extensive colitis Diagnosis of Crohn's disease (CD) or indeterminate colitis or the presence or history of a fistula consistent with CD Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etrasimod 2 mg<br> | Drug: Etrasimod<br>* Etrasimod 2 mg tablet by mouth, once daily up to 52 weeks of treatment<br>* Other names: APD334;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Etrasimod matching placebo tablet by mouth, once daily up to 52 weeks of treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Remission at Week 12 | Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily eDiary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability). Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Week 12 | 
| Percentage of Participants Achieving Clinical Remission at Week 52 | Clinical remission was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical remission was defined as SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability). Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Endoscopic Improvement at Week 12 | Endoscopic improvement was defined as an ES ≤ 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). | At Week 12 | 
| Percentage of Participants Achieving Endoscopic Improvement at Week 52 | Endoscopic improvement was defined as an ES ≤ 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). | At Week 52 | 
| Percentage of Participants Achieving Symptomatic Remission at Week 12 | Symptomatic remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline) and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. | At Week 12 | 
| Percentage of Participants Achieving Symptomatic Remission at Week 52 | Symptomatic remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline) and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. | At Week 52 | 
| Percentage of Participants With Mucosal Healing at Week 12 | Mucosal healing was defined as an ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicates more severe disease. | At Week 12 | 
| Percentage of Participants With Mucosal Healing at Week 52 | Mucosal healing was defined as an ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicates more severe disease. | At Week 52 | 
| Percentage of Participants Achieving Corticosteroid-free Clinical Remission at Week 52 | Corticosteroid-free clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, ES ≤ 1 (excluding friability), and have not received corticosteroids for ≥ 12 weeks in the 40-Week Treatment Period. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Week 52 | 
| Percentage of Participants Achieving Sustained Clinical Remission at Both Weeks 12 and 52 | Sustained clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability) at both Week 12 and Week 52. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Weeks 12 and 52 | 
| Percentage of Participants Achieving Clinical Response at Week 12 | Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB subscore ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Week 12 | 
| Percentage of Participants Achieving Clinical Response at Week 52 | Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB sub-score ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Week 52 | 
| Percentage of Participants Achieving Clinical Response at Both Weeks 12 and 52 | Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB subscore ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Weeks 12 and 52 | 
| Percentage of Participants With Mucosal Healing at Both Weeks 12 and 52 | Mucosal healing was defined as an ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicates more severe disease. | At Weeks 12 and 52 | 
| Percentage of Participants Achieving Endoscopic Normalization at Week 12 | Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease). | At Week 12 | 
| Percentage of Participants Achieving Endoscopic Normalization at Week 52 | Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease). | At Week 52 | 
| Percentage of Participants Achieving Endoscopic Normalization at Both Weeks 12 and 52 | Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease). | At Weeks 12 and 52 | 
| Percentage of Participants Achieving Symptomatic Remission by Study Visit | Symptomatic remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline) and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. | At Weeks 2, 4, 8, 16, 20, 24, 32, 40, and 48 | 
| Percentage of Participants Achieving Complete Symptomatic Remission by Study Visit | Complete symptomatic remission was defined as an SF subscore = 0 and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. | At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48 and 52 | 
| Percentage of Participants Achieving Non-invasive Clinical Response by Study Visit | Non-invasive clinical response was defined as a ≥ 30% decrease from Baseline in composite RB and SF subscores, and a ≥ 1-point decrease from Baseline in RB subscore or RB subscore ≤ 1. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease. | At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 | 
| Percentage of Participants Achieving Symptomatic Response by Study Visit | Symptomatic response was defined as a ≥ 30% decrease from Baseline in composite RB and SF subscores. The SF subscore ranged from 0 to 3 (where 0= normal number of stools and 3= at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0= no blood and 3= blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease. | At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 | 
| Percentage of Participants Achieving 4-week Corticosteroid-free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline | Four-week corticosteroid-free clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1, and have not received corticosteroids for ≥ 4 weeks in the 40-Week Treatment Period. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Week 52 | 
| Percentage of Participants Achieving Clinical Remission at Week 52 Among Participants in Clinical Response at Week 12 | Clinical remission and clinical response were based on the MMS which is a composite of 3 assessments: SF, RB and ES. Clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability). Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB subscore ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | At Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, Etrasimod, APD334