Efficacy and Safety Study of Ozanimod in Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether RPC1063 is effective in the treatment of ulcerative colitis (UC).

Official Title
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A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo Controlled Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of Induction Therapy With RPC1063 in Patients With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Ozanimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ulcerative colitis (UC) confirmed on endoscopy Moderately to severely active UC (Mayo score 6-12) Exclusion Criteria: Current use of anti-TNF agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 73 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: Ozanimod 0.5 mg<br>Participants received 0.5 mg capsules of ozanimod hydrochloride daily during the induction period weeks 0-9 (an initial 8-day dose escalation regimen in the induction period that consisted of 4 days of ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg), followed by 3 days of ozanimod HCl 0.5 mg, (equivalent to ozanimod 0.46 mg) followed by the assigned treatment level for at least 8 weeks. Participants who completed the induction period and were responders at week 8, continued to receive the same dose of ozanimod during the maintenance period up to week 32. Participants who received ozanimod 0.5 mg capsules and completed the induction period and were non-responders at Week 8 and who completed the maintenance period or experienced a disease relapse, were given the option to enter the OLP and receive 1 mg ozaninod capsules daily up to 6 years. Participants who had not shown clinical improvement 8 weeks after initiation of the OLP were discontinued from the study. | Drug: Ozanimod<br>* Ozanimod capsules by mouth daily.<br>* Other names: Zeposia, RPC 1063;|
| Experimental: Ozanimod 1 mg<br>Participants received 1 mg capsules of ozanimod hydrochloride daily during the induction period weeks 0-9 (an initial 8-day dose escalation regimen in the induction period that consisted of 4 days of ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg), followed by 3 days of ozanimod HCl 0.5 mg, (equivalent to ozanimod 0.46 mg) followed by the assigned treatment level for at least 8 weeks. Participants who completed the induction period and were responders at week 8, continued to receive the same dose of ozanimod during the maintenance period up to week 32. Participants who received ozanimod 1 mg capsules and completed the induction period and were non-responders at Week 8 and who completed the maintenance period or experienced a disease relapse, were given the option to enter the OLP and receive 1 mg ozaninod capsules daily up to 6 years. Participants who had not shown clinical improvement 8 weeks after initiation of the OLP were discontinued from the study. | Drug: Ozanimod<br>* Ozanimod capsules by mouth daily.<br>* Other names: Zeposia, RPC 1063;|
| Placebo Comparator: Placebo<br>Identically matching placebo capsules daily for 32 weeks followed by an optional open label treatment period. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Clinical Remission Based on the Central Read of the Mayo Score (MS), at Week 8 | Clinical Remission was defined as: Mayo score of <2 points and with no individual subscore of > 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. Stool Frequency Subscore (SFS) Rectal bleeding Subscore (RBS) Endoscopy Subscore Physician's Global Assessment (PGA) Clinical Remission was based on the 4-component Mayo definition. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Clinical Response in the Mayo Score (MS) at Week 8 | Clinical response was defined as a reduction from baseline in Mayo score ≥3 points and ≥30%, and a decrease from baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. Clinical Respone was based on the 4-component Mayo definition. | Week 8 | 
| Change From Baseline in Mayo Score at Week 8 | The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. Stool Frequency Subscore (SFS) Rectal bleeding Subscore (RBS) Endoscopy Subscore Physician's Global Assessment (PGA) | Baseline to Week 8 | 
| Percentage of Participants With Mucosal Healing at Week 8 | Mucosal healing is defined as an endoscopy subscore ≤ 1 point. Endoscopy subscores were calculated based on central endoscopy reading. The endoscopy scale: 0 = Normal or inactive disease = Mild disease (erythema, decreased vascular pattern, mild friability) = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) = Severe disease (spontaneous bleeding, ulceration) | Week 8 | 
| Percentage of Participants Who Achieved Clinical Remission in the Mayo Score at Week 32 | Clinical Remission was defined as: Mayo score of <2 points and with no individual subscore of > 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a score of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. Stool Frequency Subscore (SFS) Rectal bleeding Subscore (RBS) Endoscopy Subscore Physician's Global Assessment (PGA) | Week 32 | 
| Percentage of Participants Who Achieved Clinical Response at Week 32 | Clinical response was defined as a reduction from baseline in Mayo score ≥3 points and ≥30%, and a decrease from baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of ≤ 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease. Stool Frequency Subscore (SFS) Rectal bleeding Subscore (RBS) Endoscopy Subscore Physician's Global Assessment (PGA) | Week 32 | 
| Percentage of Participants With Mucosal Healing at Week 32 | Mucosal healing is defined as an endoscopy subscore ≤ 1 point. Endoscopy subscores were calculated based on central endoscopy reading. The endoscopy scale: 0 = Normal or inactive disease = Mild disease (erythema, decreased vascular pattern, mild friability) = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions) = Severe disease (spontaneous bleeding, ulceration) | Week 32 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction Period | A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities. | From the first dose of investigational product (IP) up to 90 days after the last dose of IP or at follow-up visit; the mean total duration of IP exposure was 52.8 days, 56.1 days and 50.8 days respectively for 0.5 mg, 1 mg ozanimod and placebo | 
| Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Maintenance Period | A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities. | From the first dose of IP up to 90 days after the last dose of IP or at follow-up visit; the mean total duration of IP exposure was 156.3 days, 171.1 days and 154.5 days respectively for 0.5 mg, 1 mg ozanimod and placebo. | 
| Number of Participants With TEAE During the Open-Label Treatment Period (OLP) | A TEAE was defined as any event with an onset date on or after first dose date or any ongoing event on the first dose date that worsens in severity after first dose date and until 90 days following the last dose of treatment with the study drug. earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = an AE usually transient in nature and generally not interfering with normal activities; Moderate = an AE that is sufficiently discomforting to interfere with normal activities; Severe = an AE that is incapacitating and prevents normal activities. | From the first dose of IP until 90 days after the last dose of IP or at follow-up visit; the mean total duration of study drug exposure in the OLP was 2.42 years |