To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
- Registration Number
- NCT03915769
- Lead Sponsor
- Celgene
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 195
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
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
-
Subject has clinically relevant cardiovascular conditions
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.92 mg ozanimod oral capsule QD 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. Placebo oral capsule QD Placebo 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. 0.46 mg ozanimod oral capsule once daily (QD) 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 0.46 mg ozanimod.
- Primary Outcome Measures
Name Time Method Proportion of subjects with clinical response At Week 12 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
Name Time Method Change in the EuroQol-5 Dimension (EQ-5D) from baseline At Week 12 Is a quality of life questionnaires and will be collected from all subjects at visits
Proportion of subject with clinical response At week 52 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 with clinical remission At Week 12 and Week 52 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 At Week 9 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
Proportion of subjects with endoscopic improvement At Week 12 and Week 52 Defined as an endoscopy subscore of ≤ 1 point
Proportion of subjects with mucosal healing At Week 12 and Week 52 Defined as an endoscopy subscore of ≤ 1 point and a Geboes index score \< 2.0
Proportion of subjects in remission while off corticosteroids for any length of time Up to week 52 Proportion of subjects in remission while off corticosteroids for any length of time
Adverse Event (AE) From enrollment until at least 75 days after completion of study treatment Number of participants with adverse event.
Trial Locations
- Locations (67)
Local Institution - 122
🇯🇵Chikushino, Japan
Local Institution - 119
🇯🇵Ogaki, Japan
Local Institution - 139
🇯🇵Abiko, Japan
Local Institution - 138
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 133
🇯🇵Hirosaki, Japan
Local Institution - 134
🇯🇵Isehara City, Kanagawa, Japan
Local Institution - 124
🇯🇵Fukui, Japan
Local Institution - 135
🇯🇵Kannonji, Japan
Local Institution - 160
🇯🇵Hiroshima, Japan
Local Institution - 126
🇯🇵Hitachi, Ibaraki, Japan
Local Institution - 111
🇯🇵Kurume, Fukuoka, Japan
Local Institution - 163
🇯🇵Kobe, Japan
Local Institution - 106
🇯🇵Hiroshima, Japan
Local Institution - 102
🇯🇵Sakura, Japan
Local Institution - 127
🇯🇵Osaki-shi, Japan
Local Institution - 130
🇯🇵Kobe, Japan
Local Institution - 145
🇯🇵Sakai, Japan
Local Institution - 110
🇯🇵Morioka, Japan
Local Institution - 112
🇯🇵Takamatsu, Japan
Local Institution - 143
🇯🇵Takatsuki, Japan
Local Institution - 103
🇯🇵Sapporo, Japan
Local Institution - 116
🇯🇵Saitama, Japan
Local Institution - 120
🇯🇵Kahoku-gun, Japan
Local Institution - 158
🇯🇵Kashiwa, Japan
Local Institution - 162
🇯🇵Iizuka, Japan
Local Institution - 157
🇯🇵Kawagoe, Japan
Local Institution - 165
🇯🇵Kurume, Japan
Local Institution - 141
🇯🇵Kyoto-city, Japan
Local Institution - 125
🇯🇵Nagaoka, Japan
Local Institution - 108
🇯🇵Minato-ku, Japan
Local Institution - 159
🇯🇵Oita, Japan
Local Institution - 146
🇯🇵Sendai, Japan
Local Institution - 136
🇯🇵Okayama, Japan
Local Institution - 166
🇯🇵Toshima-ku, Japan
Local Institution - 113
🇯🇵Otsu, Japan
Local Institution - 154
🇯🇵Saga, Japan
Local Institution - 117
🇯🇵Shinju-ku, Japan
Local Institution - 129
🇯🇵Toyama, Japan
Local Institution - 148
🇯🇵Utsunomiya, Japan
Local Institution - 128
🇯🇵Shinagawa-ku, Tokyo, Japan
Local Institution - 115
🇯🇵Takatsuki, Japan
Local Institution - 142
🇯🇵Kurume, Japan
Local Institution - 104
🇯🇵Sapporo, Hokkaido, Japan
Local Institution - 105
🇯🇵Nishinomiya, Hyogo, Japan
Local Institution - 153
🇯🇵Osaka-shi, Osaka, Japan
Local Institution - 132
🇯🇵Osaka, Osaka-shi, Japan
Local Institution - 156
🇯🇵Okayama-shi, Okayama, Japan
Local Institution - 150
🇯🇵Fujiidera, Japan
Local Institution - 161
🇯🇵Fukuoka, Japan
Local Institution - 131
🇯🇵Iruma-gun, Saitama, Japan
Local Institution - 164
🇯🇵Fukuoka, Japan
Local Institution - 152
🇯🇵Aki-gun, Japan
Local Institution - 155
🇯🇵Fukuoka, Japan
Local Institution - 114
🇯🇵Fukui, Japan
Local Institution - 140
🇯🇵Gifu, Japan
Local Institution - 151
🇯🇵Hakodate, Japan
Local Institution - 101
🇯🇵Kashihara, Japan
Local Institution - 121
🇯🇵Komatsu, Japan
Local Institution - 144
🇯🇵Koriyama, Japan
Local Institution - 118
🇯🇵Matsuyama, Japan
Local Institution - 107
🇯🇵Minato-ku, Japan
Local Institution - 109
🇯🇵Mitaka, Japan
Local Institution - 167
🇯🇵Nagoya-shi, Japan
Local Institution - 147
🇯🇵Sapporo, Japan
Local Institution - 149
🇯🇵Sunto-gun, Japan
Local Institution - 137
🇯🇵Shizuoka-shi, Japan
Local Institution - 123
🇯🇵Tsu, Japan