Oral Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis in Adult Japanese Participants (ELEVATE UC 40 JAPAN)

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 in adult Japanese participants with moderately to severely active ulcerative colitis (UC). This study is an extension of study APD334-302 (NCT03996369). Participants will continue with the same blinded treatment assigned in Study APD334-302 for a total treatment duration of 52 weeks (12 weeks in Study APD334-302 plus 40 weeks in Study APD334-308).

Official Title
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A Phase 3, Double-Blind, Placebo-Controlled, 40-Week Extension Study to Assess the Efficacy and Safety of Etrasimod in Japanese 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: Participants with moderately to severely active ulcerative colitis (UC) are eligible to enroll into this study if they fulfill all of the following: Must have completed the Week 12 visit of Study APD334-302 Ability to provide written informed consent or assent (parent or legal guardian must provide consent for a participant < 20 years of age or as required per local regulations who has assented to participate in the study) and to be compliant with the schedule of protocol assessments. Enrollment of participants < 20 years should be conducted only if acceptable according to local laws and regulations. Both men and women subjects agree to use a highly effective method of birth control if the possibility of conception exists Exclusion Criteria: Participants who meet any of the following exclusion criteria will not be eligible for enrollment into the study: If the Investigator considers the participant to be unsuitable for any reason to participate in the study Participants requiring partial or total colectomy during the APD334-302 study Participants requiring treatment with prohibited concomitant medications

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<br>* Other names: APD334;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Etrasimod matching placebo tablet by mouth, once daily up to 52 weeks<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 40 of Study APD334-308 | 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 electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to [>=] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | Week 40 of APD334-308 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Endoscopic Improvement at Week 40 of Study APD334-308 | Endoscopic improvement was defined as an ES <=1 (excluding friability) at Week 40 of APD334-308 compared with Week 12 of APD334-302. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease); higher score indicated more severe disease. | Week 40 of APD334-308 | 
| Percentage of Participants Achieving Symptomatic Remission at Week 40 of Study APD334-308 | Symptomatic remission was defined as an SF sub-score = 0 (or = 1 with a >= 1 point decrease from Baseline) and RB sub-score = 0. The SF sub-score ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB sub-score ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicated more severe disease. | Week 40 of APD334-308 | 
| Percentage of Participants With Mucosal Healing at Week 40 of Study APD334-308 | Mucosal healing was defined as an ES <= 1 (excluding friability) with histologic remission measured by a Geboes Index score less than [<] 2.0). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system, was 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 indicated more severe disease. | Week 40 of APD334-308 | 
| Percentage of Participants, Who Had Not Been Receiving Corticosteroids for ≥ 12 Weeks, Achieving Clinical Remission at Week 40 of Study APD334-308 Among Participants Receiving Corticosteroids at C5041015 (APD334-302) Study Entry | 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 electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to [>=] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. | Week 40 of APD334-308 | 
| Percentage of Participants Achieving Sustained Clinical Remission | 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 electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to [>=] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. A subject with sustained clinical remission is defined as someone who achieved clinical remission at both Week 12 of APD334-302 and Week 40 of APD334-308. | Week 40 of APD334-308 | 

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