A Placebo-Controlled Study of Oral Ozanimod as Maintenance Therapy for Moderately to Severely Active Crohn's Disease

• ClinicalTrials.gov Identifier: NCT03464097
• Recruitment Status: Recruiting
• First Posted: March 13, 2018
• Last Update Posted: May 23, 2023
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: February 26, 2018
• First Posted Date: March 13, 2018
• Last Update Posted Date: May 23, 2023
• Actual Study Start Date: June 27, 2018
• Estimated Primary Completion Date: March 24, 2025 (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 of < 150 [ Time Frame: Weekk 52 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD
• Proportion of participants with a Simple Endoscopic Score for Crohn's Disease (SES-CD) score decrease from baseline of ≥ 50% [ Time Frame: Week 52 ]

Original Primary Outcome Measures (submitted: March 12, 2018)

• Proportion of subjects with a CDAI score of < 150 at Week 40 [ Time Frame: Up to approximately week 40 ]
  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 a Simple Endoscopic Score for Crohn's Disease (SES-CD) score decrease from baseline of ≥ 50% at Week 40 [ Time Frame: Up to approximately week 40 ]
  The simple endoscopy score (SES-CD) assesses the degree of endoscopic inflammation.

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

• Proportion of participants with CDAI reduction from baseline of ≥ 100 points or CDAI score of < 150 [ Time Frame: Week 52 ]
• Proportion of participants with average daily abdominal pain score ≤ 1 point and average daily stoolfrequency ≤ 3 points with abdominal pain and stool frequency no worse than baseline [ Time Frame: Week 52 ]
• Proportion of participants with a CDAI score < 150 at Week 52, while remaining corticosteroid-free in the prior 12 weeks [ Time Frame: Week 52 ]
• Proportion of participants with a CDAI score of < 150 in participants with a CDAI score < 150 at pre-randomization [ Time Frame: Week 52 ]
• Proportion of participants with a CDAI score of < 150 at Week 52 and at ≥ 80% of visits between Week 8 and Week 52, inclusive, in participants with a CDAI score <150 at pre-randomization [ Time Frame: Week 52 ]
• Proportion of participants with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥ 10% at Week 52 [ Time Frame: Week 52 ]
• Histologic improvement based on differences between ozanimod and placebo in histologic diseaseactivity scores (ie, Global Histologic Disease Activity Score [GHAS] changes) [ Time Frame: Week 52 ]
• Proportion of participants with average daily abdominal pain score ≤ 1 point, with average daily stool frequency score ≤ 3 points with abdominal pain and stool frequency no worse than baseline and an SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 52 ]
• Proportion of participants with CDAI score of < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 52 ]
• Proportion of participants with average daily abdominal pain score ≤ 1 point, with average daily stoolfrequency score ≤ 3 points with abdominal pain and stool frequency no worse than baseline and an SES-CD ≤ 4 points and a SES-CD decrease ≥2 points [ Time Frame: Week 52 ]
• Proportion of participants with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 with SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 52 ]
• Proportion of participants with CDAI score < 150 at Week 12 and SES-CD decrease from baseline of ≥50% [ Time Frame: Week 52 ]
• Proportion of participants with CDAI reduction from baseline of ≥ 70 points [ Time Frame: Week 52 ]
• Proportion of participants with mucosal healing (SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points) with histologic improvement by GHAS or Robarts Histologic Index [ Time Frame: Week 52 ]
• Time to relapse and exclusion of other causes of an increase in disease activity unrelated tounderlying CD (eg, infections, change in medication) [ Time Frame: Week 52 ]
• Proportion of participants with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% [ Time Frame: Week 52 ]

Original Secondary Outcome Measures (submitted: March 12, 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 40. [ Time Frame: Up to approximately week 40 ]
  Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary.
• Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score of < 150 at Week 40 [ Time Frame: Up to approximately week 40 ]
  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 a CDAI score of < 150 at both pre-randomization and Week 40 [ Time Frame: Up to approximately week 40 ]
  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 a CDAI score of < 150 at Week 40 in subjects in with a CDAI score < 150 at pre-randomization [ Time Frame: Up to approximately week 40 ]
  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 a CDAI score < 150 in subjects off corticosteroids at Week 40 [ Time Frame: Up to approximately week 40 ]
  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 40 [ Time Frame: Up to approximately week 40 ]
  Ulcer size will be measured during endoscopy, and 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 40 [ Time Frame: Up to approximately week 40 ]
  Global Histologic Disease Activity score is a measure of histologic inflammation.
• Proportion of subjects with CDAI score of < 150 and SES-CD decrease from baseline of ≥ 50% at Week 40 [ Time Frame: Up to approximately week 40 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD. The simple endoscopy score (SES-CD) assesses the degree of endoscopic inflammation.
• Proportion of subjects with CDAI reduction from baseline of ≥ 70 points at Week 40 [ Time Frame: Up to approximately week 40 ]
  The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
• Mucosal healing at Week 40 [ Time Frame: Up to approximately week 40 ]
  Mucosal healing is measured by histologic inflammation
• Time to relapse [ Time Frame: Up to approximately week 40 ]
  Relapse will be assessed by endoscopy and clinical symptoms
• Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% at Week 52 [ Time Frame: Up to approximately week 52 ]
  CDEIS (Crohn's Disease Endoscopic Index of Severity) is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. CDEIS score considers 4 parameters (deep ulcerations, superficial ulcerations, surface involved by disease, and surface involved by ulcerations), each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score can be calculated even in case of incomplete investigations, as the results of the individual segments are divided by the number of segments investigated. The presence of stenosis, as a result of ulcer or not, increases the score at the end of the computation.
• Improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores [ Time Frame: Up to approximately week 40 ]
  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 40 ]
  The medical outcomes SF-36 questionnaire provides a measure of the subject's health status.
• Improvement in Work Productivity and Activity Impairment questionnaire for Crohn's disease (WPAI)-CD scores [ Time Frame: Up to approximately week 40 ]
  The WPAI-CD is a validated, reliable and responsive instrument that assesses the impact of CD on work and activity.
• Improvement in EuroQol five dimensions questionnaire (EQ-5D) scores [ Time Frame: Up to approximately week 40 ]
  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 40 ]
  The number of Crohn's disease related hospitalizations, surgeries, and procedures will be collected by counting healthcare resource utilization encounters, and comparing them and assessing the cost differences between ozanimod and placebo

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

Descriptive Information

• Brief Title: A Placebo-Controlled Study of Oral Ozanimod as Maintenance Therapy for Moderately to Severely Active Crohn's Disease
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Maintenance Therapy for Moderately to Severely Active Crohn's Disease
• Brief Summary: This is a study to demonstrate the effect of oral ozanimod as maintenance therapy in 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: Ozanimod
  Intervention: Drug: Ozanimod
• Placebo Comparator: 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: March 12, 2018): 485
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 24, 2025
• Estimated Primary Completion Date: March 24, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit: www.BMSStudyConnect.com

Inclusion Criteria:

• Fulfilled the inclusion criteria at time of entry into the induction study and completed the week 12 efficacy assessments of the induction study
• In clinical response and/or clinical remission and/or an average daily stool frequency score ≤ 3 and an average abdominal pain score ≤ 1 with abdominal pain and stool frequency no worse than baseline at Week 12 of the Induction Study

Exclusion Criteria:

• Partial or total colectomy, small bowel resection, or an ostomy since day 1 of the induction studies or has developed a symptomatic fistula
• Had a rectal steroid therapy, rectal 5-aminosalicylates, parenteral corticosteroids, immunomodulatory agents, investigational agents or apheresis

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: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information,; please email:; Clinical.Trials@bms.com

Contact: First line of the email MUST contain the NCT# and Site #.

• Listed Location Countries: Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Mexico, Moldova, Republic of, Netherlands, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Senegal, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Brazil, Norway

Administrative Information

• NCT Number: NCT03464097
• Other Study ID Numbers: RPC01-3203; U1111-1203-8002 ( Registry Identifier: WHO ); 2017-004294-14 ( 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