To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

Study Overview
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Brief Summary
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Japanese patients with moderate or severe active ulcerative colitis as a subject when ozanimod 0.46 mg or 0.92 mg is orally administered is evaluated about dose response, efficacy and safety with placebo as a control.

Detailed Description
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Following the up to 5-week Screening Period, eligible subjects will be randomized to enter the 12 weeks placebo-controlled Induction Period (IP). Subjects who are responders at Week 12 will continue on their assigned treatment in the 40-week Maintenance Period (MP). Non responders at Week 12 have the option to enter the Open-label Extension (OLE). Subjects who complete the MP will be given the option to participate in the OLE. Subjects that enter the MP and experience disease relapse will also have the option to enter the OLE. The OLE will continue until marketing launch (about 4 years of ozanimod for Ulcerative colitis (UC), or until the Sponsor discontinues the development program.

Official Title
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A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of Oral Ozanimod to Evaluate Efficacy and Long-term Safety in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Ozanimod
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Main Inclusion Criteria for Induction and Maintenance Periods Subject is a Japanese male or female subjects aged 18 to 75 years at the time of signing the informed consent form (ICF) at Screening. Subject has had Ulcerative Colitis (UC) diagnosed at least 3 months prior to first investigational product administration. The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histopathology report. Subject has evidence of UC extending ≥ 15 cm from the anal verge as determined by Baseline endoscopy (flexible sigmoidoscopy or colonoscopy). Subject has active UC defined as Mayo score of 6 to 12 inclusive, with endoscopic subscore of ≥ 2, a rectal bleeding score of ≥ 1, and a stool frequency score ≥ 1. Main Inclusion Criteria for Open-label Extension Period Subjects must satisfy the following criteria to be enrolled in the study: Must have completed the Week 12 Visit and is non-responder at Week 12 Who completes the IP and enters the MP, completes participation through the last study treatment visit at Week 52 with maintaining clinical response, OR experiences disease relapse during the MP Exclusion Criteria: Main Exclusion Criteria Subject has severe extensive colitis Subject has diagnosis of Crohn's disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn's disease or microscopic colitis or radiation colitis or ischemic colitis. Subject has positive stool examination for pathogens (ova and parasites, bacteria) or positive test for toxin producing Clostridium difficile (C. difficile) at Screening.4. Subject is pregnant or breastfeeding 5. Subject has clinically relevant cardiovascular conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.46 mg ozanimod oral capsule once daily (QD)<br>It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with 0.23 mg ozanimod, followed by 3 days of treatment with 0.46 mg ozanimod, followed by 0.46 mg ozanimod. | Drug: Ozanimod<br>* Ozanimod is an orally bioavailable, small molecule compound that activates the sphingosine 1-phosphate 1 receptor (S1P1) and the S1P 5 receptor (S1P5), although it is more selective towards S1P1 over S1P5<br>|
| Experimental: 0.92 mg ozanimod oral capsule QD<br>It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with 0.23 mg ozanimod, followed by 3 days of treatment with 0.46 mg ozanimod, followed by 0.92 mg ozanimod. | Drug: Ozanimod<br>* Ozanimod is an orally bioavailable, small molecule compound that activates the sphingosine 1-phosphate 1 receptor (S1P1) and the S1P 5 receptor (S1P5), although it is more selective towards S1P1 over S1P5<br>|
| Placebo Comparator: Placebo oral capsule QD<br>It will be a 7-day dose escalation regimen in the IP consisting of 4 days of treatment with a placebo capsule, followed by 3 days of treatment with two placebo capsules, followed by two placebo capsules. | Other: Placebo<br>* The placebo is a capsule that contains no study medication but looks exactly like the study medication capsule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with clinical response | Defined as a reduction from Baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from Baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point | At Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with clinical remission | Defined as: Definition 1. Complete Mayo score of ≤ 2 points with no individual subscore of > 1 point, Definition 2. Rectal bleeding subscore = 0 and stool frequency subscore ≤ 1 (and a decrease of ≥ 1 point from the Baseline stool frequency subscore) and endoscopy subscore ≤ 1 | At Week 12 and Week 52 | 
| Proportion of subjects with a clinical response | Defined as a reduction from Baseline in the 9-point Mayo score of ≥ 2 points and ≥ 35%, and a reduction from Baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point | At Week 12 and Week 52 | 
| Proportion of subjects with endoscopic improvement | Defined as an endoscopy subscore of ≤ 1 point | At Week 12 and Week 52 | 
| Proportion of subjects with mucosal healing | Defined as an endoscopy subscore of ≤ 1 point and a Geboes index score < 2.0 | At Week 12 and Week 52 | 
| Proportion of subjects with a clinical response | Defined as a reduction from Baseline in the partial Mayo score of ≥ 2 points and ≥ 30%, and a reduction from Baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point | At Week 9 | 
| Change in the EuroQol-5 Dimension (EQ-5D) from baseline | Is a quality of life questionnaires and will be collected from all subjects at visits | At Week 12 | 
| Proportion of subject with clinical response | Defined as a reduction from Baseline in the complete Mayo score of ≥ 3 points and ≥ 30%, and a reduction from Baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point | At week 52 | 
| Proportion of subjects in remission while off corticosteroids for any length of time | Proportion of subjects in remission while off corticosteroids for any length of time | Up to week 52 | 
| Adverse Event (AE) | Number of participants with adverse event. | From enrollment until at least 75 days after completion of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative, Ulcerative colitis, Ozanimod, colitis