Induction Study #1 of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease

• ClinicalTrials.gov Identifier: NCT03440372
• Recruitment Status: Recruiting
• First Posted: February 22, 2018
• Last Update Posted: May 23, 2023
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: February 14, 2018
• First Posted Date: February 22, 2018
• Last Update Posted Date: May 23, 2023
• Actual Study Start Date: February 27, 2018
• Estimated Primary Completion Date: March 22, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 15, 2021): Proportion of participants with a Crohn's Disease Activity Index (CDAI) score < 150 [ Time Frame: Week 12 ]

Original Primary Outcome Measures (submitted: February 14, 2018)

Proportion of subjects with a CDAI score < 150 at Week 12 [ Time Frame: Up to approximately week 12 ]

The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.

Current Secondary Outcome Measures (submitted: November 15, 2021)

• Proportion of participants with average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points with abdominal pain and stool frequency no worse than baseline [ Time Frame: Week 12 ]
• Proportion of participants with a Simple Endoscopic Score for Crohn's Disease (SES-CD) score decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
• Proportion of participants with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 [ Time Frame: Week 12 ]
• Proportion of participants with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
• Proportion of participants with CDAI score < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
• Proportion of participants with an average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points and both no worse than baseline AND an SES-CD ≤ 4 points and decrease ≥2 points [ Time Frame: Week 12 ]
• Proportion of participants with an average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points and both no worse than baseline AND an SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
• Histologic Improvement based on differences between ozanimod and placebo in histologic disease activity scores (ie, Global Histologic Disease Activity Score changes) [ Time Frame: Week 12 ]
• Proportion of participants with CDAI reduction from baseline of ≥ 70 points [ Time Frame: Week 12 ]
• Proportion of participants with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥ 10% [ Time Frame: Week 12 ]
• Proportion of participants with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]

Original Secondary Outcome Measures (submitted: February 14, 2018)

• Proportion of subjects with average daily abdominal pain score ≤ 1 point, average daily stool frequency score ≤ 3, and stool frequency no worse than baseline at week 12. [ Time Frame: Up to approximately week 12 ]
  Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary.
• Proportion of subjects with a Simple Endoscopic Score for Crohn's Disease (SES-CD) decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
  The SES-CD assesses the degree of endoscopic inflammation.
• Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 at Week 12 [ Time Frame: Up to approximately week 12 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
• Proportion of subjects with CDAI reduction from baseline of ≥ 100 points with SES-CD decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD and the SES-CD assesses the degree of endoscopic inflammation.
• Proportion of subjects with CDAI score < 150 with SES-CD decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD and the SES-CD assesses the degree of endoscopic inflammation.
• Proportion of subjects with CDAI score <150 at Week 12 and SES-CD decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD and the SES-CD assesses the degree of endoscopic inflammation.
• Proportion of subjects with histological improvement (ie. as measured by Global Histologic Disease Activity score changes (Geboes, 2000) at Week 12 [ Time Frame: Up to approximately week 12 ]
  Global Histologic Disease Activity score is a measure of histologic inflammation.
• Proportion of subjects with CDAI reduction from baseline of ≥ 70 points at Week 12 [ Time Frame: Up to approximately week 12 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
• Proportion of subjects with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥10% at Week 12 [ Time Frame: Up to approximately week 12 ]
  Ulcer size will be measured during endoscopy, and assesses the degree of endoscopic inflammation.
• Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
  The CDEIS assesses the degree of endoscopic inflammation.
• Improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores [ Time Frame: Up to approximately week 12 ]
  The IBDQ is a frequently used outcome parameter in clinical trials. The IBDQ is a responsive instrument for reflection quick change in the quality of life of patients with CD, within a 2-week period. The IBDQ has evolved into a standard for measuring disease-specific quality of life in patients with CD.
• Improvement in 36-Item Short Form-36 Survey (SF-36) scores [ Time Frame: Up to approximately week 12 ]
  The medical outcomes SF-36 questionnaire provides a measure of the subject's health status.
• Improvement in Work Productivity and Activity Impairment Questionnaire (WPAI)-CD scores [ Time Frame: Up to approximately week 12 ]
  The WPAI-CD is a validated, reliable and responsive instrument that assesses the impact of CD on work and activity.
• Improvement in EuroQol 5 dimensions questionnaire (EQ-5D) scores [ Time Frame: Up to approximately week 12 ]
  The EQ-5D is a validated, 6-item, self-administered instrument designed to measure generic health status.
• Differences in CD-related hospitalizations and surgery [ Time Frame: Up to approximately week 12 ]
  Healthcare Resource Utilization (HRU) will be evaluated in this study to assess the impact of CD on healthcare utilization.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Induction Study #1 of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease
• Official Title: Induction Study #1 - A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease
• Brief Summary: This is a study to explore the effect of oral ozanimod as an induction treatment for participants with moderately to severely active Crohn's Disease.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn Disease

Intervention

• Drug: Ozanimod
  Specified dose on specified days
• Other: Placebo
  Specified dose on specified days

Study Arms

• Experimental: Administration of oral Ozanimod
  Intervention: Drug: Ozanimod
• Placebo Comparator: Administration of Placebo
  Intervention: Other: Placebo

• Publications *: Feagan BG, Schreiber S, Afzali A, Rieder F, Hyams J, Kollengode K, Pearlman J, Son V, Marta C, Wolf DC, D'Haens GG. Ozanimod as a novel oral small molecule therapy for the treatment of Crohn's disease: The YELLOWSTONE clinical trial program. Contemp Clin Trials. 2022 Nov;122:106958. doi: 10.1016/j.cct.2022.106958. Epub 2022 Oct 5.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 14, 2018): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 28, 2024
• Estimated Primary Completion Date: March 22, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Crohn's disease for ≥ 3 months on endoscopy and on histological exam
• Inadequate response or loss of response to corticosteroids, immunomodulators, and/or biologic therapies
• Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450
• An average daily stool frequency ≥ 4 points and/or an abdominal pain of ≥ 2 points
• Has Simple Endoscopic Score for Crohn's Disease (SES-CD) score of ≥ 6 (or SES-CD ≥ 4 in participants with isolated ileal disease)

Exclusion Criteria:

• Has a diagnosis of ulcerative colitis, indeterminate colitis, radiation colitis, or ischemic colitis, or has strictures with prestenotic dilatation requiring procedural intervention
• Has extensive small bowel resection (>100cm) or known diagnosis of short bowel syndrome, or requires total parenteral nutrition
• Current stoma, ileal-anal pouch anastomosis, or fistula

Other protocol-defined inclusion/exclusion criteria apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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 #.

• Listed Location Countries: Argentina, Australia, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Chile, Croatia, Czechia, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Korea, Republic of, Latvia, Mexico, Moldova, Republic of, Poland, Romania, Russian Federation, Saudi Arabia, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Brazil, Norway

Administrative Information

• NCT Number: NCT03440372
• Other Study ID Numbers: RPC01-3201; U1111-1203-7225 ( Registry Identifier: WHO ); 2017-004292-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Celgene
• Original Responsible Party: Same as current
• Current Study Sponsor: Celgene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Celgene
• Verification Date: May 2023