|
|
| To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis |
| Clinicaltrials.gov identifier | recruitment status | First Posted | Last update posted |
| NCT03915769 | Recruiting | April 16, 2019 | February 8, 2022 |
|
|
| 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. |
| Condition or Disease: | Colitis, Ulcerative |
| Intervention/treatment: |
Drug: Ozanimod Other: Placebo |
| Phase: | Phase 3 |
| Detailed Description |
|
Following the 4-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 52-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. |
|
|
| study design | ||||||||||||||||||||
|
|
|
| Arms and interventions |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: 0.46 mg ozanimod oral capsule once daily (QD) 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 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 |
|
Experimental: 0.92 mg ozanimod oral capsule QD 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 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 |
|
Placebo Comparator: Placebo oral capsule QD 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 The placebo is a capsule that contains no study medication but looks exactly like the study medication capsule. |
| outcome measures |
| Primary Outcome Measures: |
1. Proportion of subjects with clinical response [ Time Frame: 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: |
1. Proportion of subjects with clinical remission [ Time Frame: 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 |
|
2. Proportion of subjects in clinical remission measured at week 12- Rectal Bleeding [ Time Frame: Up to week 12 ] Defined as 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 |
|
|
3. Proportion of subjects with endoscopic improvement [ Time Frame: At Week 12 and Week 52 ] Defined as an endoscopy subscore of ≤ 1 point |
|
|
4. Proportion of subjects with mucosal healing [ Time Frame: At Week 12 and Week 52 ] Defined as an endoscopy subscore of ≤ 1 point and a Geboes index score < 2.0 |
|
|
5. Proportion of subjects with a clinical response [ Time Frame: 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 |
|
|
6. Change in the EuroQol-5 Dimension (EQ-5D) from baseline [ Time Frame: At Week 12 ] Is a quality of life questionnaires and will be collected from all subjects at visits |
|
|
7. Proportion of subjects in clinical remission measured at week 52 - Mayo Score [ Time Frame: Up to week 52 ] Complete Mayo score of ≤ 2 points with no individual subscore of > 1 point |
|
|
8. Proportion of subject with clinical response [ Time Frame: 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 |
|
|
9. Proportion of subjects in remission while off corticosteroids for any length of time [ Time Frame: Up to week 52 ] Proportion of subjects in remission while off corticosteroids for any length of time |
|
|
10. Change in partial Mayo score from Baseline [ Time Frame: Up to week 64 ] Change in partial Mayo score from Baseline |
|
|
11. Adverse Event (AE) [ Time Frame: From enrollment until at least 75 days after completion of study treatment ] Number of participants with adverse event. |
|
|
12. Proportion of subjects in clinical remission measured at week 52- Rectal Bleeding [ Time Frame: Up to week 52 ] Defined as an endoscopy subscore of ≤ 1 point |
|
|
13. Proportion of subject with clinical response at week 52 [ Time Frame: Up to 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 |
|
|
14. Proportion of subjects with endoscopic improvement [ Time Frame: Up to week 52 ] Defined as an endoscopy subscore of ≤ 1 point |
|
|
15. Proportion of subjects with mucosal healing [ Time Frame: Up to week 52 ] Defined as an endoscopy subscore of ≤ 1 point and a Geboes index score < 2.0 |
|
|
| Eligibility Criteria |
| Ages Eligible for Study: | 18 to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| 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 |
|
|
| Contacts and Locations |
| Contacts |
|
Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com Contact: First line of the email MUST contain the NCT# and Site #. |
| Locations |
| Japan | Kokikai Tokatsu-Tsujinaka Hospital | Abiko |
| Japan | Mazda Hospital of Mazda Motor Corporation | Aki-gun |
| Japan | Tokyo Medical and Dental University Hospital | Bunkyo-ku |
| Japan | Fukuoka University Chikushi Hospital | Chikushino |
| Japan | Sai Clinic | Fujiidera |
| Japan | Fukui Prefectural Hospital | Fukui |
| Japan | Fukui-ken Saiseikai Hospital | Fukui |
| Japan | Saiseikai Fukuoka General Hospital | Fukuoka |
| Japan | Harasanshin Hospital | Fukuoka |
| Japan | Japanese Red Cross Fukuoka Hospital | Fukuoka |
| Japan | Gifu Prefectural General Medical Center | Gifu |
| Japan | Hakodate Goryokaku Hospital | Hakodate |
| Japan | Hirosaki University Hospital | Hirosaki |
| Japan | Hiroshima Prefectural Hospital | Hiroshima |
| Japan | Hiroshima University Hospital | Hiroshima |
| Japan | Hitachi General Hospital | Hitachi, Ibaraki |
| Japan | Aso Iizuka Hospital | Iizuka |
| Japan | Saitama Medical University Hospital | Iruma-gun |
| Japan | Tokai University Hospital | Isehara City, Kanagawa |
| Japan | Kanazawa Medical University Hospital | Kahoku-gun |
| Japan | Mitoyo General Hospital | Kannonji |
| Japan | Nara Medical University Hospital | Kashihara |
| Japan | Tsujinaka Hospital Kashiwanoha | Kashiwa |
| Japan | Saitama Medical Center | Kawagoe |
| Japan | Medical Corporation Aoyama Clinic | Kobe |
| Japan | Kobe University Hospital | Kobe |
| Japan | Komatsu Municipal Hospital | Komatsu |
| Japan | Hoshi General Hospital | Koriyama |
| Japan | Kurume University Hospital | Kurume, Fukuoka |
| Japan | Our Lady of the Snow Social Medical Corporation St. Mary's Hospital | Kurume |
| Japan | Hidaka Coloproctology Clinic | Kurume |
| Japan | University Hospital, Kyoto Prefectural University of Medicine | Kyoto-city |
| Japan | Ehime Prefectural Central Hospital | Matsuyama |
| Japan | Jikei University Hospital | Minato-ku |
| Japan | Kitasato University Kitasato Institute Hospital | Minato-ku |
| Japan | Kyorin University Hospital | Mitaka |
| Japan | Iwate Medical University Uchimaru Medical Center | Morioka |
| Japan | Nagaoka Chuo General Hospital | Nagaoka |
| Japan | Nagoya University Hospital | Nagoya-shi |
| Japan | Hyogo College of Medicine Hospital | Nishinomiya |
| Japan | Ogaki Municipal Hospital | Ogaki |
| Japan | Ishida Clinic of IBD and Gastroenterology | Oita |
| Japan | Okayama Saiseikai Outpatient Center Hospital | Okayama |
| Japan | Okayama University Hospital | Okayama |
| Japan | Iseikai Hospital | Osaka |
| Japan | Osaka City University Hospital | Osaka |
| Japan | Osaki Citizen Hospital | Osaki-shi |
| Japan | Shiga University of Medical Science Hospital | Otsu |
| Japan | Saga University Hospital | Saga |
| Japan | Tokitokai Tokito Clinic | Saitama |
| Japan | Osaka Rosai Hospital | Sakai |
| Japan | Toho University Medical Center Sakura Hospital | Sakura |
| Japan | Sapporo Medical University Hospital | Sapporo, Hokkaidô |
| Japan | JA Sapporo Kosei General Hospital | Sapporo |
| Japan | Japan Community Health care Organization Hokkaido Hospital | Sapporo |
| Japan | IMS Meirikai Sendai General Hospital | Sendai |
| Japan | NTT Medical Center Tokyo | Shinagawa-ku, Tokyo |
| Japan | Tokyo Yamate Medical Center | Shinju-ku |
| Japan | Shizuoka City Shizuoka Hospital | Shizuoka-shi |
| Japan | National Hospital Organization Shizuoka Medical Center | Sunto-gun |
| Japan | Kagawa Prefectural Central Hospital | Takamatsu |
| Japan | Medical Corporation Shoyu-Kai Fujita Gastroenterology Hospital | Takatsuki |
| Japan | Takatsuki Red Cross Hospital | Takatsuki |
| Japan | Hiratsuka Gastroenterological hospital | Toshima-ku |
| Japan | Toyama City Hospital | Toyama |
| Japan | Mie University hospital | Tsu |
| Japan | Kanke Gastrointestinal Clinic | Utsunomiya |
| Sponsors and Collaborators |
| Celgene |
| Investigator | ||
| Study Director : | Bristol-Myers Squibb | Bristol-Myers Squibb |
| More Information | |||||||||||||
| Responsible Party : | Celgene | ||||||||||||
| ClinicalTrials.gov Identifier : | NCT03915769 | ||||||||||||
| Other Study ID Numbers : | RPC01-3103, U1111-1230-3228 | ||||||||||||
| First Posted : | April 16, 2019 | ||||||||||||
| Last Update Posted : | February 8, 2022 | ||||||||||||
| Last Verified : | February 2022 | ||||||||||||
|
Individual Participant Data (IPD) Sharing Statement: |
|||||||||||||
| Plan to Share IPD: | Yes | ||||||||||||
| Plan Description: | https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/ | ||||||||||||
| Supporting Materials: | Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code | ||||||||||||
| Time Frame: | See Plan Description | ||||||||||||
| Access Criteria: | See Plan Description | ||||||||||||
| URL: | https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/ | ||||||||||||
| 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 | ||||||||||||
| Keywords provided by Celgene: |
Ulcerative colitis Ozanimod colitis Ulcerative |
||||||||||||
| Additional relevant MeSH terms : |
|