Back to resultsTo Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
Primary Purpose
Colitis, Ulcerative
Status
Active
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Ozanimod
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Colitis, Ulcerative focused on measuring Ulcerative colitis, Ozanimod, colitis, Ulcerative
Eligibility Criteria
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:
1. Subject must have completed through the Week 12 Visit in the Induction Period (IP) AND either:
- Completed participation through the last study treatment visit at Week 64 and maintained clinical response in the Maintenance Period (MP), OR
- Experiencing disease relapse eligible for Open-label Extension (OLE).
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
Sites / Locations
- Local Institution - 105
- Local Institution - 156
- Local Institution - 132
- Local Institution - 131
- Local Institution - 138
- Local Institution - 139
- Local Institution - 152
- Local Institution - 122
- Local Institution - 150
- Local Institution - 114
- Local Institution - 161
- Local Institution - 164
- Local Institution - 155
- Local Institution - 140
- Local Institution - 151
- Local Institution - 160
- Local Institution - 106
- Local Institution - 126
- Local Institution - 134
- Local Institution - 120
- Local Institution - 135
- Local Institution - 101
- Local Institution - 158
- Local Institution - 157
- Local Institution - 163
- Local Institution - 130
- Local Institution - 121
- Local Institution - 144
- Local Institution - 111
- Local Institution - 142
- Local Institution - 165
- Local Institution - 141
- Local Institution - 118
- Local Institution - 108
- Local Institution - 107
- Local Institution - 109
- Local Institution - 110
- Local Institution - 125
- Local Institution - 167
- Local Institution - 119
- Local Institution - 159
- Local Institution - 136
- Local Institution - 153
- Local Institution - 113
- Local Institution - 154
- Local Institution - 116
- Local Institution - 145
- Local Institution - 102
- Local Institution - 104
- Local Institution - 103
- Local Institution - 147
- Local Institution - 128
- Local Institution - 117
- Local Institution - 137
- Local Institution - 149
- Local Institution - 112
- Local Institution - 115
- Local Institution - 143
- Local Institution - 166
- Local Institution - 129
- Local Institution - 123
- Local Institution - 148
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
0.46 mg ozanimod oral capsule once daily (QD)
0.92 mg ozanimod oral capsule QD
Placebo oral capsule QD
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
Proportion of subjects with endoscopic improvement
Defined as an endoscopy subscore of ≤ 1 point
Proportion of subjects with mucosal healing
Defined as an endoscopy subscore of ≤ 1 point and a Geboes index score < 2.0
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
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
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
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
Adverse Event (AE)
Number of participants with adverse event.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03915769
Brief Title
To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 3, 2019 (Actual)
Primary Completion Date
March 13, 2025 (Anticipated)
Study Completion Date
March 13, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colitis, Ulcerative
Keywords
Ulcerative colitis, Ozanimod, colitis, Ulcerative
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
195 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
0.46 mg ozanimod oral capsule once daily (QD)
Arm Type
Experimental
Arm Description
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.
Arm Title
0.92 mg ozanimod oral capsule QD
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo oral capsule QD
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ozanimod
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The placebo is a capsule that contains no study medication but looks exactly like the study medication capsule.
Primary Outcome Measure Information:
Title
Proportion of subjects with clinical response
Description
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
Time Frame
At Week 12
Secondary Outcome Measure Information:
Title
Proportion of subjects with clinical remission
Description
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
Time Frame
At Week 12 and Week 52
Title
Proportion of subjects with a clinical response
Description
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
Time Frame
At Week 12 and Week 52
Title
Proportion of subjects with endoscopic improvement
Description
Defined as an endoscopy subscore of ≤ 1 point
Time Frame
At Week 12 and Week 52
Title
Proportion of subjects with mucosal healing
Description
Defined as an endoscopy subscore of ≤ 1 point and a Geboes index score < 2.0
Time Frame
At Week 12 and Week 52
Title
Proportion of subjects with a clinical response
Description
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
Time Frame
At Week 9
Title
Change in the EuroQol-5 Dimension (EQ-5D) from baseline
Description
Is a quality of life questionnaires and will be collected from all subjects at visits
Time Frame
At Week 12
Title
Proportion of subject with clinical response
Description
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
Time Frame
At week 52
Title
Proportion of subjects in remission while off corticosteroids for any length of time
Description
Proportion of subjects in remission while off corticosteroids for any length of time
Time Frame
Up to week 52
Title
Adverse Event (AE)
Description
Number of participants with adverse event.
Time Frame
From enrollment until at least 75 days after completion of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution - 105
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
Local Institution - 156
City
Okayama-shi
State/Province
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Local Institution - 132
City
Osaka
State/Province
Osaka-shi
ZIP/Postal Code
545-8586
Country
Japan
Facility Name
Local Institution - 131
City
Iruma-gun
State/Province
Saitama
ZIP/Postal Code
3500495
Country
Japan
Facility Name
Local Institution - 138
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8519
Country
Japan
Facility Name
Local Institution - 139
City
Abiko
ZIP/Postal Code
270-1168
Country
Japan
Facility Name
Local Institution - 152
City
Aki-gun
ZIP/Postal Code
735-8585
Country
Japan
Facility Name
Local Institution - 122
City
Chikushino
ZIP/Postal Code
818-8502
Country
Japan
Facility Name
Local Institution - 150
City
Fujiidera
ZIP/Postal Code
538-0027
Country
Japan
Facility Name
Local Institution - 114
City
Fukui
ZIP/Postal Code
910-8526
Country
Japan
Facility Name
Local Institution - 161
City
Fukuoka
ZIP/Postal Code
810-0001
Country
Japan
Facility Name
Local Institution - 164
City
Fukuoka
ZIP/Postal Code
812-0033
Country
Japan
Facility Name
Local Institution - 155
City
Fukuoka
ZIP/Postal Code
815-8555
Country
Japan
Facility Name
Local Institution - 140
City
Gifu
ZIP/Postal Code
500-8717
Country
Japan
Facility Name
Local Institution - 151
City
Hakodate
ZIP/Postal Code
040-8611
Country
Japan
Facility Name
Local Institution - 160
City
Hiroshima
ZIP/Postal Code
734-8530
Country
Japan
Facility Name
Local Institution - 106
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Local Institution - 126
City
Hitachi, Ibaraki
ZIP/Postal Code
317-0077
Country
Japan
Facility Name
Local Institution - 134
City
Isehara City, Kanagawa
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
Local Institution - 120
City
Kahoku-gun
ZIP/Postal Code
920-0293
Country
Japan
Facility Name
Local Institution - 135
City
Kannonji
ZIP/Postal Code
769-1695
Country
Japan
Facility Name
Local Institution - 101
City
Kashihara
ZIP/Postal Code
634-8522
Country
Japan
Facility Name
Local Institution - 158
City
Kashiwa
ZIP/Postal Code
277-0871
Country
Japan
Facility Name
Local Institution - 157
City
Kawagoe
ZIP/Postal Code
350-8550
Country
Japan
Facility Name
Local Institution - 163
City
Kobe
ZIP/Postal Code
650-0015
Country
Japan
Facility Name
Local Institution - 130
City
Kobe
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Local Institution - 121
City
Komatsu
ZIP/Postal Code
923-8560
Country
Japan
Facility Name
Local Institution - 144
City
Koriyama
ZIP/Postal Code
963-8501
Country
Japan
Facility Name
Local Institution - 111
City
Kurume, Fukuoka
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
Local Institution - 142
City
Kurume
ZIP/Postal Code
830-8543
Country
Japan
Facility Name
Local Institution - 165
City
Kurume
ZIP/Postal Code
839-0809
Country
Japan
Facility Name
Local Institution - 141
City
Kyoto-city
ZIP/Postal Code
602-8566
Country
Japan
Facility Name
Local Institution - 118
City
Matsuyama
ZIP/Postal Code
790-0024
Country
Japan
Facility Name
Local Institution - 108
City
Minato-ku
ZIP/Postal Code
105-8471
Country
Japan
Facility Name
Local Institution - 107
City
Minato-ku
ZIP/Postal Code
108-8642
Country
Japan
Facility Name
Local Institution - 109
City
Mitaka
ZIP/Postal Code
181-8611
Country
Japan
Facility Name
Local Institution - 110
City
Morioka
ZIP/Postal Code
020-8505
Country
Japan
Facility Name
Local Institution - 125
City
Nagaoka
ZIP/Postal Code
940-8653
Country
Japan
Facility Name
Local Institution - 167
City
Nagoya-shi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
Local Institution - 119
City
Ogaki
ZIP/Postal Code
503-8502
Country
Japan
Facility Name
Local Institution - 159
City
Oita
ZIP/Postal Code
870-0823
Country
Japan
Facility Name
Local Institution - 136
City
Okayama
ZIP/Postal Code
700-0013
Country
Japan
Facility Name
Local Institution - 153
City
Osaka
ZIP/Postal Code
533-0022
Country
Japan
Facility Name
Local Institution - 113
City
Otsu
ZIP/Postal Code
520-2192
Country
Japan
Facility Name
Local Institution - 154
City
Saga
ZIP/Postal Code
849-8501
Country
Japan
Facility Name
Local Institution - 116
City
Saitama
ZIP/Postal Code
336-0963
Country
Japan
Facility Name
Local Institution - 145
City
Sakai
ZIP/Postal Code
591-8025
Country
Japan
Facility Name
Local Institution - 102
City
Sakura
ZIP/Postal Code
285-8741
Country
Japan
Facility Name
Local Institution - 104
City
Sapporo, Hokkaidô
ZIP/Postal Code
060-8543
Country
Japan
Facility Name
Local Institution - 103
City
Sapporo
ZIP/Postal Code
060-0033
Country
Japan
Facility Name
Local Institution - 147
City
Sapporo
ZIP/Postal Code
062-8618
Country
Japan
Facility Name
Local Institution - 128
City
Shinagawa-ku, Tokyo
ZIP/Postal Code
141-8625
Country
Japan
Facility Name
Local Institution - 117
City
Shinju-ku
ZIP/Postal Code
169-0073
Country
Japan
Facility Name
Local Institution - 137
City
Shizuoka-shi
ZIP/Postal Code
420-8630
Country
Japan
Facility Name
Local Institution - 149
City
Sunto-gun
ZIP/Postal Code
411-8611
Country
Japan
Facility Name
Local Institution - 112
City
Takamatsu
ZIP/Postal Code
760-8557
Country
Japan
Facility Name
Local Institution - 115
City
Takatsuki
ZIP/Postal Code
569-0086
Country
Japan
Facility Name
Local Institution - 143
City
Takatsuki
ZIP/Postal Code
569-1096
Country
Japan
Facility Name
Local Institution - 166
City
Toshima-ku
ZIP/Postal Code
171-0021
Country
Japan
Facility Name
Local Institution - 129
City
Toyama
ZIP/Postal Code
939-8511
Country
Japan
Facility Name
Local Institution - 123
City
Tsu
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
Local Institution - 148
City
Utsunomiya
ZIP/Postal Code
320-0003
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
IPD Sharing Time Frame
See Plan Description
IPD Sharing Access Criteria
See Plan Description
IPD Sharing URL
https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls
URL
http://www.BMSStudyConnect.com
Description
BMS Clinical Trial Patient Recruiting
Learn more about this trial
To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
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