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To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT03915769
Recruitment Status : Not yet recruiting
First Posted : April 16, 2019
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: Ozanimod Other: Placebo Phase 2 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 195 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 26, 2019
Estimated Primary Completion Date : October 30, 2021
Estimated Study Completion Date : November 30, 2023

Resource links provided by the National Library of Medicine


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.




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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years 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

  1. 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.
  2. 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.
  3. Subject has evidence of UC extending ≥ 15 cm from the anal verge as determined by Baseline endoscopy (flexible sigmoidoscopy or colonoscopy).
  4. 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

  1. Subject has severe extensive colitis
  2. 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.
  3. 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03915769


Contacts
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Contact: Eijiro Higashi +81-3-5224-0892 ehigashi@celgene.com
Contact: Aya Nagshima +81-3-5224-0788 anagashima@celgene.com

Sponsors and Collaborators
Celgene
Investigators
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Study Director: Ben Hatano, MD, PhD Celgene

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03915769     History of Changes
Other Study ID Numbers: RPC01-3103
U1111-1230-3228 ( Registry Identifier: WHO )
First Posted: April 16, 2019    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
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/

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