Safety and Efficacy of Etrasimod (APD334) in Patients With Ulcerative Colitis

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

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study to Investigate the Safety and Efficacy of APD334 in Patients 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: Moderately to severely active ulcerative colitis defined as a 3-component Mayo Clinic score Evidence of colonic ulcerative colitis activity on endoscopy Exclusion Criteria: Within 30 days prior to randomization, receipt of any of the following for the treatment of underlying disease: Non-biologic therapies (eg, cyclosporine, tacrolimus, tofacitinib, thalidomide), a non-biologic investigational therapy or an approved non-biologic therapy in an investigational protocol Within 60 days prior to randomization, receipt of any of the following: Infliximab, adalimumab, golimumab, certolizumab, vedolizumab, any other investigational or approved biologic agent Any prior exposure to natalizumab, efalizumab, or rituximab

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etrasimod Low Dose<br>Oral, low dose, daily for 12 Weeks | Drug: Etrasimod<br> <br> * Other names: APD334;|
| Experimental: Etrasimod High Dose<br>Oral, high dose, daily for 12 weeks | Drug: Etrasimod<br> <br> * Other names: APD334;|
| Placebo Comparator: Placebo<br>Oral, placebo, daily for 12 weeks. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Adapted Mayo Score (MCS) at Week 12 | The adapted MCS was used to measure disease activity of ulcerative colitis. It consisted of 3 subscores (stool frequency, rectal bleeding, and findings of endoscopy), each of which was rated on a scale from 0 to 3, indicating normal to severe. The adapted MCS was calculated as the sum of the 3 subscores, and the overall score values ranged from 0 to 9, with a higher score indicating more severe disease. Multiple imputation method was used to handle missing data. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Endoscopic Improvement at Week 12 | For determination of the endoscopic subscore of the MCS, a flexible proctosigmoidoscopy, performed with a videoendoscope following a cleansing prep (oral or rectal cathartic) was performed at screening (within 10 days prior to administration of the first dose of study drug) and the Week 12 visit. This efficacy procedure assessed endoscopic mucosal appearance. The results were rated on a scale from 0 to 3, indicating normal to severe. Endoscopic improvement was defined as Mayo endoscopic subscore (using findings of flexible proctosigmoidoscopy) of ≤1 point. Multiple imputation method was used to handle missing data. | Week 12 | 
| Change From Baseline in 2-component MCS at Week 12 | The 2-component MCS was used to measure disease activity of ulcerative colitis. It consisted of 2 subscores (rectal bleeding and findings on endoscopy), each of which was rated on a scale from 0 to 3, indicating normal to severe. The 2-component MCS was calculated as the sum of the 2 subscores, and the overall score value ranged from 0 to 6, with a higher score indicating more severe disease. Multiple imputation method was used to handle missing data. | Baseline and Week 12 | 
| Change From Baseline in Total Mayo Score (TMS) at Week 12 | The TMS was used to measure disease activity of ulcerative colitis. It consisted of 4 subscores [stool frequency, rectal bleeding, findings of endoscopy (flexible proctosigmoidoscopy), and Physician's Global Assessment (PGA) score], each of which was rated on a scale from 0 to 3, indicating normal to severe. The TMS was calculated as the sum of the 4 subscores, and the overall score values ranged from 0 to 12, with a higher score indicating more severe disease. Multiple imputation method was used to handle missing data. | Baseline and Week 12 |