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

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: Placebo
Drug: Etrasimod

Registration Number: NCT03945188

Lead Sponsor: Arena Pharmaceuticals

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 433

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Etrasimod 2 mg	Etrasimod	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Clinical Remission at Week 12	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.
Percentage of Participants Achieving Clinical Remission at Week 52	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Endoscopic Improvement at Week 12	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).
Percentage of Participants Achieving Symptomatic Remission at Week 52	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.
Percentage of Participants With Mucosal Healing at Week 12	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.
Percentage of Participants Achieving Symptomatic Remission at Week 12	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.
Percentage of Participants With Mucosal Healing at Both Weeks 12 and 52	At 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.
Percentage of Participants Achieving Symptomatic Remission by Study Visit	At Weeks 2, 4, 8, 16, 20, 24, 32, 40, and 48	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.
Percentage of Participants Achieving Clinical Response at Week 52	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.
Percentage of Participants Achieving Clinical Response at Both Weeks 12 and 52	At 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.
Percentage of Participants Achieving Endoscopic Normalization at Week 12	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).
Percentage of Participants Achieving Non-invasive Clinical Response by Study Visit	At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	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.
Percentage of Participants With Mucosal Healing at Week 52	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.
Percentage of Participants Achieving Sustained Clinical Remission at Both Weeks 12 and 52	At 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.
Percentage of Participants Achieving Clinical Response at Week 12	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.
Percentage of Participants Achieving Endoscopic Normalization at Week 52	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).
Percentage of Participants Achieving Endoscopic Normalization at Both Weeks 12 and 52	At 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).
Percentage of Participants Achieving Complete Symptomatic Remission by Study Visit	At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48 and 52	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.
Percentage of Participants Achieving Symptomatic Response by Study Visit	At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52	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.
Percentage of Participants Achieving Clinical Remission at Week 52 Among Participants in Clinical Response at Week 12	At Week 52	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.
Percentage of Participants Achieving Corticosteroid-free Clinical Remission at Week 52	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.
Percentage of Participants Achieving 4-week Corticosteroid-free Clinical Remission at Week 52 Among Participants Receiving Corticosteroids at Baseline	At Week 52	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.
Percentage of Participants Achieving Endoscopic Improvement at Week 52	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).

Trial Locations

Locations (312): Digestive Health Specialists of the Southeast
🇺🇸
Dothan, Alabama, United States
Arizona Digestive Health
🇺🇸
Sun City, Arizona, United States
Om Research, LLC
🇺🇸
Lancaster, California, United States
Entertainment Medical Group, Inc.
🇺🇸
Los Angeles, California, United States
United Medical Doctors
🇺🇸
Murrieta, California, United States
San Diego Gastroenterology Medical Associates
🇺🇸
San Diego, California, United States
ACRC Studies, LLC
🇺🇸
San Diego, California, United States
Peak Gastroenterology Associates
🇺🇸
Colorado Springs, Colorado, United States
Gastro Florida
🇺🇸
Clearwater, Florida, United States
West Central Gastroenterology d/b/a Gastro Florida
🇺🇸
Clearwater, Florida, United States
Scroll for more (302 remaining)
Digestive Health Specialists of the Southeast
🇺🇸Dothan, Alabama, United States