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
Study Type: Interventional
Estimated Enrollment : 195 participants
Intervention Model : Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
Actual Study Start Date: June 2019
Estimated Primary Completion Date: February 2023
Estimated Study Completion Date: March 2025

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 :
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases