CClinicalTrials.gg
CompletedNCT03440385Updated Dec 5, 2024Results posted

Induction Study #2 of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease

A Phase 3 interventional study of Ozanimod and Placebo in Crohn Disease, sponsored by Celgene. Completed at 368 sites in 31 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-12-05.

Sponsored by Celgene · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
606
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Crohn Disease

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Keywords

  • Crohn's Disease
  • Crohn Disease
  • Oral
  • Ozanimod
  • Moderately active
  • Severely active
  • RPC01
  • RPC01-3202
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

Inclusion 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 therapy
  • Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450
  • Average daily stool frequency ≥ 4 points and/or an abdominal pain of ≥ 2 points
  • Simple Endoscopic Score for Crohn's Disease (SES-CD) score of ≥ 6 (or SES-CD ≥ 4 in participants with isolated ileal disease)

Exclusion criteria

Exclusion Criteria:

  • Diagnosis of ulcerative colitis, indeterminate colitis, radiation colitis, or ischemic colitis, or has strictures with prestenotic dilatation requiring procedural intervention
  • 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

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
606 participants (actual)

Study arms

  • Experimental
    Administration of oral Ozanimod

    Drug: Ozanimod

  • Placebo comparator
    Administration of Placebo

    Other: Placebo

Interventions

  • DrugOzanimod

    Specified dose on specified days

  • OtherPlacebo

    Specified dose on specified days

05

What researchers measure

Primary outcomes

  1. Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 150

    The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease (CD). The CDAI uses a questionnaire with 8 disease activity variables: number of soft/liquid stools, severity of abdominal pain, general well-being, presence of complications, need for antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. The sub scores of number of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

    Time frame: Week 12

Secondary outcomes

  1. Percentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission

    Abdominal pain and stool frequency clinical remission was defined as average daily abdominal pain score ≤ 1 point, and average daily stool frequency ≤ 3 with abdominal pain and stool frequency no worse than baseline at Week 12. Participants entered the responses in diaries daily. The 7 days entries prior to Week 12 visit were considered for calculating average abdominal pain score and stool frequency. The abdominal pain was graded on severity of 0 (none) to 3 (severe) scale and stool frequency was defined number of liquid or soft stools per day. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

    Time frame: Week 12

  2. Percentage of Participants With a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%

    The SES-CD assessed the degree of inflammation. The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater degree of inflammation. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

    Time frame: Week 12

  3. Percentage of Participants With Reduction From Baseline in the Crohn's Disease Activity Index (CDAI) Score of >= 100 Points or a Total CDAI Score < 150

    The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease (CD). The CDAI uses a questionnaire with 8 disease activity variables: number of soft/liquid stools, severity of abdominal pain, general well-being, presence of complications, need for antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. The sub scores of number of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

    Time frame: Week 12

  4. Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score Reduction From Baseline of ≥ 100 Points or CDAI Score < 150 and SES-CD Decrease From Baseline of ≥ 50%

    CDAI include 8 components number of soft/liquid stools, severity of abdominal pain, wellbeing, complications, need antidiarrheal drugs, abdominal mass, hematocrit, deviation in body wt. Subscores of numbers of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to visit. The others weighted to create the total CDAI score ranging 0-600 with higher score indicating worse outcome. The SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). In SES-CD, each of 4 components are assessed in the five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

    Time frame: Week 12

  5. Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 150 and Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%

    CDAI include 8 components number of soft/liquid stools, severity of abdominal pain, wellbeing, complications, need antidiarrheal drugs, abdominal mass, hematocrit, deviation in body wt. Subscores of numbers of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to visit. The others weighted to create the total CDAI score ranging 0-600 with higher score indicating worse outcome. The SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). In SES-CD, each of 4 components are assessed in the five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

    Time frame: Week 12

  6. Percentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission and a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score <= 4 Points and Decrease >= 2 Points

    Abdominal pain (AP) and stool frequency (SF) clinical remission was defined as average daily abdominal pain score ≤ 1 point, and average daily stool frequency ≤ 3 times with AP and SF no worse than baseline at Week 12. Participants entered responses in diaries daily. The 7 days entries prior to visit were considered for calculating average AP score and SF. The AP was graded on severity of 0 (none) to 3 (severe) scale and SF was defined number of liquid or soft stools per day. The SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). In SES-CD, each of 4 components are assessed in the five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

    Time frame: Week 12

  7. Percentage of Participants With Global Histologic Activity Score (GHAS) Remission

    GHAS assesses the inflammation and mucosal damage. GHAS has 8 components Epithelial damage, Architectural changes, Infiltration of mononuclear cells in the lamina propria, Infiltration of polymorphonuclear cells in the lamina propria, Polymorphonuclear cells in epithelium, Presence of erosion and/or ulcers, Presence of granuloma and number of biopsy specimens affected. Each of these components was scored on a scale of 0 (none/unaffected) to 2 (worst). Each of these 8 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. Within each segment, the GHAS score has a range of 0 - 16, and the total GHAS score has a range of 0 - 80. Higher numbers correspond to more inflammation and more mucosal damage. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

    Time frame: Week 12

  8. Percentage of Participants With CDAI Reduction From Baseline of >=70 Points

    The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease (CD). The CDAI uses a questionnaire with 8 disease activity variables: number of soft/liquid stools, severity of abdominal pain, general well-being, presence of complications, need for antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. The sub scores of number of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

    Time frame: Week 12

  9. Percentage of Participants With Absence of Ulcers ≥ 0.5 cm With no Segment With Any Ulcerated Surface ≥10%

    The ulcerated surface were assessed via endoscopy.

    Time frame: Week 12

  10. Percentage of Participants With a Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of ≥ 50%

    CDEIS is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. The CDEIS divides the intestine into 5 segments: rectum, sigmoid and left colon, transverse colon, right colon, and ileum. Four variables are assessed in each segment: the presence of deep ulceration, the presence of superficial ulceration, the percentage of ulcerated surface, and the percentage of surface affected by CD, indicated on 10-cm visual analogue scales. In addition, the presence of ulcerated stenosis and the presence of nonulcerated stenosis are also assessed over the entire intestine. These factors are weighted and summed to calculate the total score ranging from 0- 44, with higher scores indicating more severe disease.

    Time frame: Week 12

  11. Percentage of Participants With Abdominal Pain (AP) and Stool Frequency (SF) Clinical Remission and an Endoscopic (50%) Response

    AP and SF clinical remission is average daily abdominal pain score ≤ 1 point, and average daily stool frequency ≤ 3 times with AP and SF no worse than baseline at Week 12. Participants entered responses in diaries daily. The 7 days entries prior to visit were considered for calculating average AP score and SF. AP was graded on severity of 0 (none) to 3 (severe) scale and SF was defined number of liquid or soft stools per day. SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). Endoscopic Response is defined as \>= 50% decrease from baseline in SES-CD. In SES-CD, each of 4 components are assessed in five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was sum of individual scores of each of components across five segments. Range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

    Time frame: Week 12

  12. Percentage of Participants With Robarts Histologic Index (RHI) Mucosal Healing at Week 12

    RHI mucosal healing was defined as RHI remission combined with SES-CD \<= 4 points and a SES-CD decrease from baseline \>= 2 points with no SES-CD sub-score \>1 point. RHI Remission is defined as no active inflammation in any measured segment. The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater degree of inflammation.

    Time frame: Week 12

06

Results

Posted Dec 5, 2024

Participant flow

Participant flow — Overall Study
MilestoneOzanimodPlacebo
Started403203
Safety population404202
Completed360183
Not completed4320
Withdrew: Other reason41
Withdrew: Site closed10
Withdrew: Lost to follow-up20
Withdrew: Withdrawal by subject126
Withdrew: Lack of efficacy92
Withdrew: Adverse event1511

Outcome measures

PrimaryPercentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 150

The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease (CD). The CDAI uses a questionnaire with 8 disease activity variables: number of soft/liquid stools, severity of abdominal pain, general well-being, presence of complications, need for antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. The sub scores of number of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 150
percentage of participantsOzanimodPlacebo
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 15029.830.5
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.8125 · Odds ratio (or): 0.96 · 95% CI 0.66 to 1.39Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission

Abdominal pain and stool frequency clinical remission was defined as average daily abdominal pain score ≤ 1 point, and average daily stool frequency ≤ 3 with abdominal pain and stool frequency no worse than baseline at Week 12. Participants entered the responses in diaries daily. The 7 days entries prior to Week 12 visit were considered for calculating average abdominal pain score and stool frequency. The abdominal pain was graded on severity of 0 (none) to 3 (severe) scale and stool frequency was defined number of liquid or soft stools per day. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission
percentage of participantsOzanimodPlacebo
Percentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission29.026.6
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.5400 · Odds ratio (or): 1.13 · 95% CI 0.77 to 1.66Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%

The SES-CD assessed the degree of inflammation. The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater degree of inflammation. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%
percentage of participantsOzanimodPlacebo
Percentage of Participants With a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%25.621.2
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.2411 · Odds ratio (or): 1.28 · 95% CI 0.85 to 1.95Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With Reduction From Baseline in the Crohn's Disease Activity Index (CDAI) Score of >= 100 Points or a Total CDAI Score < 150

The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease (CD). The CDAI uses a questionnaire with 8 disease activity variables: number of soft/liquid stools, severity of abdominal pain, general well-being, presence of complications, need for antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. The sub scores of number of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Reduction From Baseline in the Crohn's Disease Activity Index (CDAI) Score of >= 100 Points or a Total CDAI Score < 150
percentage of participantsOzanimodPlacebo
Percentage of Participants With Reduction From Baseline in the Crohn's Disease Activity Index (CDAI) Score of >= 100 Points or a Total CDAI Score < 15046.247.3
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.7469 · Odds ratio (or): 0.94 · 95% CI 0.67 to 1.34Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With Crohn's Disease Activity Index (CDAI) Score Reduction From Baseline of ≥ 100 Points or CDAI Score < 150 and SES-CD Decrease From Baseline of ≥ 50%

CDAI include 8 components number of soft/liquid stools, severity of abdominal pain, wellbeing, complications, need antidiarrheal drugs, abdominal mass, hematocrit, deviation in body wt. Subscores of numbers of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to visit. The others weighted to create the total CDAI score ranging 0-600 with higher score indicating worse outcome. The SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). In SES-CD, each of 4 components are assessed in the five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score Reduction From Baseline of ≥ 100 Points or CDAI Score < 150 and SES-CD Decrease From Baseline of ≥ 50%
percentage of participantsOzanimodPlacebo
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score Reduction From Baseline of ≥ 100 Points or CDAI Score < 150 and SES-CD Decrease From Baseline of ≥ 50%16.914.3
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.4255 · Odds ratio (or): 1.22 · 95% CI 0.75 to 1.97Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 150 and Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%

CDAI include 8 components number of soft/liquid stools, severity of abdominal pain, wellbeing, complications, need antidiarrheal drugs, abdominal mass, hematocrit, deviation in body wt. Subscores of numbers of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to visit. The others weighted to create the total CDAI score ranging 0-600 with higher score indicating worse outcome. The SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). In SES-CD, each of 4 components are assessed in the five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 150 and Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%
percentage of participantsOzanimodPlacebo
Percentage of Participants With Crohn's Disease Activity Index (CDAI) Score < 150 and Simple Endoscopic Score for Crohn's Disease (SES-CD) Score Decrease From Baseline of ≥ 50%11.711.3
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.9313 · Odds ratio (or): 1.02 · 95% CI 0.60 to 1.76Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission and a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score <= 4 Points and Decrease >= 2 Points

Abdominal pain (AP) and stool frequency (SF) clinical remission was defined as average daily abdominal pain score ≤ 1 point, and average daily stool frequency ≤ 3 times with AP and SF no worse than baseline at Week 12. Participants entered responses in diaries daily. The 7 days entries prior to visit were considered for calculating average AP score and SF. The AP was graded on severity of 0 (none) to 3 (severe) scale and SF was defined number of liquid or soft stools per day. The SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). In SES-CD, each of 4 components are assessed in the five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission and a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score <= 4 Points and Decrease >= 2 Points
percentage of participantsOzanimodPlacebo
Percentage of Participants With Abdominal Pain and Stool Frequency Clinical Remission and a Simple Endoscopic Score for Crohn's Disease (SES-CD) Score <= 4 Points and Decrease >= 2 Points10.48.4
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.4339 · Odds ratio (or): 1.27 · 95% CI 0.70 to 2.31Odds ratio and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With Global Histologic Activity Score (GHAS) Remission

GHAS assesses the inflammation and mucosal damage. GHAS has 8 components Epithelial damage, Architectural changes, Infiltration of mononuclear cells in the lamina propria, Infiltration of polymorphonuclear cells in the lamina propria, Polymorphonuclear cells in epithelium, Presence of erosion and/or ulcers, Presence of granuloma and number of biopsy specimens affected. Each of these components was scored on a scale of 0 (none/unaffected) to 2 (worst). Each of these 8 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. Within each segment, the GHAS score has a range of 0 - 16, and the total GHAS score has a range of 0 - 80. Higher numbers correspond to more inflammation and more mucosal damage. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Global Histologic Activity Score (GHAS) Remission
percentage of participantsOzanimodPlacebo
Percentage of Participants With Global Histologic Activity Score (GHAS) Remission13.610.8
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.3330 · Odds ratio (or): 1.30 · 95% CI 0.77 to 2.20Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With CDAI Reduction From Baseline of >=70 Points

The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease (CD). The CDAI uses a questionnaire with 8 disease activity variables: number of soft/liquid stools, severity of abdominal pain, general well-being, presence of complications, need for antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. The sub scores of number of soft/liquid stool, severity of abdominal pain (0 \[none\] to 3 \[Severe\]), general well-being (0 \[well\] to 4 \[terrible\] were summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome. Baseline was defined as the last assessment prior to the start time of the first drug administration if time of measurement is available else the last assessment prior to or on the date of the first drug administration.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With CDAI Reduction From Baseline of >=70 Points
percentage of participantsOzanimodPlacebo
Percentage of Participants With CDAI Reduction From Baseline of >=70 Points52.951.7
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.8200 · Odds ratio (or): 1.04 · 95% CI 0.74 to 1.47Odds ratio and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With Absence of Ulcers ≥ 0.5 cm With no Segment With Any Ulcerated Surface ≥10%

The ulcerated surface were assessed via endoscopy.

Time frame:
Week 12
Reported as:
Number · percentage of partiicpants
Percentage of Participants With Absence of Ulcers ≥ 0.5 cm With no Segment With Any Ulcerated Surface ≥10%
percentage of partiicpantsOzanimodPlacebo
Percentage of Participants With Absence of Ulcers ≥ 0.5 cm With no Segment With Any Ulcerated Surface ≥10%25.324.1
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.7776 · Odds ratio (or): 1.06 · 95% CI 0.71 to 1.59Odds ratio and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).
SecondaryPercentage of Participants With a Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of ≥ 50%

CDEIS is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. The CDEIS divides the intestine into 5 segments: rectum, sigmoid and left colon, transverse colon, right colon, and ileum. Four variables are assessed in each segment: the presence of deep ulceration, the presence of superficial ulceration, the percentage of ulcerated surface, and the percentage of surface affected by CD, indicated on 10-cm visual analogue scales. In addition, the presence of ulcerated stenosis and the presence of nonulcerated stenosis are also assessed over the entire intestine. These factors are weighted and summed to calculate the total score ranging from 0- 44, with higher scores indicating more severe disease.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With a Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of ≥ 50%
percentage of participantsOzanimodPlacebo
Percentage of Participants With a Crohn's Disease Endoscopic Index of Severity (CDEIS) Decrease From Baseline of ≥ 50%27.521.7
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.1187 · Odds ratio (or): 1.39 · 95% CI 0.92 to 2.11Odds ratio and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no)
SecondaryPercentage of Participants With Abdominal Pain (AP) and Stool Frequency (SF) Clinical Remission and an Endoscopic (50%) Response

AP and SF clinical remission is average daily abdominal pain score ≤ 1 point, and average daily stool frequency ≤ 3 times with AP and SF no worse than baseline at Week 12. Participants entered responses in diaries daily. The 7 days entries prior to visit were considered for calculating average AP score and SF. AP was graded on severity of 0 (none) to 3 (severe) scale and SF was defined number of liquid or soft stools per day. SES-CD has 4 components size of ulcers, ulcerated surface, affected surface, presence of narrowing. Each component was scored on scale of 0 (none) to 3 (worst). Endoscopic Response is defined as \>= 50% decrease from baseline in SES-CD. In SES-CD, each of 4 components are assessed in five segments: ileum, right, transverse, left colon, and rectum. The SES-CD was sum of individual scores of each of components across five segments. Range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for overall, with larger scores show greater degree of inflammation.

Time frame:
Week 12
Reported as:
Number · percentage of particpants
Percentage of Participants With Abdominal Pain (AP) and Stool Frequency (SF) Clinical Remission and an Endoscopic (50%) Response
percentage of particpantsOzanimodPlacebo
Percentage of Participants With Abdominal Pain (AP) and Stool Frequency (SF) Clinical Remission and an Endoscopic (50%) Response11.79.4
Statistical analysis
  • Ozanimod vs Placebo · Cochran-Mantel-Haenszel · p = 0.4030 · Odds ratio (or): 1.28 · 95% CI 0.72 to 2.26Odds ratio and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no)
SecondaryPercentage of Participants With Robarts Histologic Index (RHI) Mucosal Healing at Week 12

RHI mucosal healing was defined as RHI remission combined with SES-CD \<= 4 points and a SES-CD decrease from baseline \>= 2 points with no SES-CD sub-score \>1 point. RHI Remission is defined as no active inflammation in any measured segment. The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater degree of inflammation.

Time frame:
Week 12
Reported as:
Number · percentage of participants
Percentage of Participants With Robarts Histologic Index (RHI) Mucosal Healing at Week 12
percentage of participantsOzanimodPlacebo
Percentage of Participants With Robarts Histologic Index (RHI) Mucosal Healing at Week 124.04.9
Statistical analysis
  • Ozanimod vs Placebo · Mantel Haenszel · p = 0.5630 · Odds ratio (or): 0.79 · 95% CI 0.35 to 1.78Odds ratio, and p-value are obtained using the CMH test stratified by corticosteroid use at baseline (yes or no), and prior biologic use (yes or no).

Adverse events

Collected over All cause mortality, non serious adverse events and serious adverse events were collected from the first dose and up to approximately 31 weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ozanimod0/404 (0%)24/404 (5.9%)15/404 (3.7%)
Placebo0/202 (0%)11/202 (5.4%)11/202 (5.4%)
Most frequent serious events
Showing 10 of 25
Most frequent serious events
EventOzanimodPlacebo
Crohn's diseaseGastrointestinal disorders10/4046/202
Small intestinal obstructionGastrointestinal disorders4/4040/202
PericarditisCardiac disorders0/4041/202
Abdominal painGastrointestinal disorders2/4040/202
Colonic fistulaGastrointestinal disorders0/4041/202
ProctitisGastrointestinal disorders0/4041/202
Abdominal wall abscessInfections and infestations0/4041/202
GastroenteritisInfections and infestations0/4041/202
Incision site haematomaInjury, poisoning and procedural complications0/4041/202
Rash papularSkin and subcutaneous tissue disorders0/4041/202
Most frequent other events
Most frequent other events
EventOzanimodPlacebo
Crohn's diseaseGastrointestinal disorders15/40411/202

Baseline characteristics

Age, Continuous
Age, Continuous(years)OzanimodPlaceboTotal
Mean39.8 ± 13.6937.7 ± 13.7939.1 ± 13.75
Sex: Female, Male
Sex: Female, Male(Participants)OzanimodPlaceboTotal
Female18290272
Male221113334
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)OzanimodPlaceboTotal
Hispanic or Latino131225
Not Hispanic or Latino378188566
Unknown or Not Reported12315
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)OzanimodPlaceboTotal
WHITE329166495
BLACK OR AFRICAN AMERICAN718
AMERICAN INDIAN OR ALASKA NATIVE101
ASIAN472976
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER101
OTHER8412
NOT REPORTED10313
07

Study locations

368 sites
  • Local Institution - 202
    Scottsdale, Arizona 85258, United States
  • Ucsd Medical Center
    La Jolla, California 92037, United States
  • Local Institution - 010
    Lancaster, California 93534, United States
  • Southern California Research Institute Medical Group, Inc.
    Los Angeles, California 90045, United States
  • Matrix Clinical Research Inc
    Los Angeles, California 90048, United States
  • Facey Medical Foundation (Parent)
    Mission Hills, California 91345, United States
  • Local Institution - 093
    Pasadena, California 91105, United States
  • Sutter Medical Group
    Roseville, California 95661, United States
  • Local Institution - 280
    Sacramento, California 95817, United States
  • Local Institution - 281
    San Francisco, California 94158, United States
  • Local Institution - 124
    West Covina, California 91790, United States
  • Local Institution - 065
    Colorado Springs, Colorado 80907, United States
  • Local Institution - 182
    Bristol, Connecticut 06010, United States
  • Local Institution - 166
    Clearwater, Florida 33765, United States
  • Local Institution - 084
    Clermont, Florida 34711, United States
  • American Research Institute Inc
    Cutler Bay, Florida 33157, United States
  • Local Institution - 112
    Doral, Florida 33166, United States
  • Riverside Clinical Research
    Edgewater, Florida 32132, United States
  • SIH Research
    Kissimmee, Florida 34759, United States
  • Local Institution - 067
    Lighthouse Point, Florida 33064, United States
  • Center For Advanced Gastroenterology
    Maitland, Florida 32751, United States
  • Local Institution - 044
    Miami Springs, Florida 33166, United States
  • LMG Research
    Miami, Florida 33125, United States
  • Local Institution - 175
    Miami, Florida 33166, United States
  • Local Institution - 081
    Miami, Florida 33176, United States
  • Local Institution - 192
    New Port Richey, Florida 34655, United States
  • Local Institution - 200
    Orlando, Florida 32810, United States
  • Local Institution - 002
    Palmetto Bay, Florida 33157, United States
  • Theia Clinical Research, LLC
    Pinellas Park, Florida 33781, United States
  • Precision Clinical Research, LLC.
    Sunrise, Florida 33351, United States
  • Local Institution - 183
    Tampa, Florida 33612-4799, United States
  • Apex Clinical Research
    Tampa, Florida 33612, United States
  • Local Institution - 107
    Tampa, Florida 33614, United States
  • Local Institution - 037
    Atlanta, Georgia 30322, United States
  • Local Institution - 220
    Atlanta, Georgia 30322, United States
  • Local Institution - 143
    Decatur, Georgia 30030, United States
  • Local Institution - 115
    Idaho Falls, Idaho 83404, United States
  • Local Institution - 022
    Chicago, Illinois 60637, United States
  • Local Institution - 092
    Evansville, Indiana 47714, United States
  • Local Institution - 033
    Indianapolis, Indiana 46202, United States
  • Local Institution - 070
    Topeka, Kansas 66606, United States
  • Local Institution - 020
    Baton Rouge, Louisiana 70809, United States
  • Clinical Trials of SW Louisiana LLC
    Lake Charles, Louisiana 70601, United States
  • Tandem Clinical Research, LLC
    Marrero, Louisiana 70072, United States
  • Local Institution - 024
    Worcester, Massachusetts 01655, United States
  • Local Institution - 167
    Kalamazoo, Michigan 49008, United States
  • Local Institution - 005
    Novi, Michigan 48377, United States
  • Local Institution - 095
    Minneapolis, Minnesota 55455, United States
  • Local Institution - 045
    Rochester, Minnesota 55905, United States
  • Local Institution - 198
    Kansas City, Missouri 64111, United States
  • Internal Medicine Specialists
    Las Vegas, Nevada 89145, United States
  • Local Institution - 040
    Lebanon, New Hampshire 03756, United States
  • Local Institution - 054
    Hartsdale, New York 10530, United States
  • Weill Cornell Medical College
    New York, New York 10010, United States
  • Concorde Medical Group
    New York, New York 10016, United States
  • TrialSpark
    New York, New York 10024, United States
  • Local Institution - 060
    North Massapequa, New York 11758-1802, United States
  • Local Institution - 156
    Charlotte, North Carolina 28209, United States
  • Local Institution - 052
    Winston-Salem, North Carolina 27103, United States
  • Local Institution - 170
    Dayton, Ohio 45417, United States
  • Local Institution - 049
    Hilliard, Ohio 43026, United States
  • Paramount Medical Research & Consulting, Llc
    Middleburg Heights, Ohio 44130, United States
  • Local Institution - 087
    Norman, Oklahoma 73071, United States
  • Local Institution - 294
    Oklahoma City, Oklahoma 73102, United States
  • Local Institution - 185
    Tulsa, Oklahoma 74136, United States
  • Local Institution - 217
    Tulsa, Oklahoma 74137, United States
  • University of Pennsylvania Cancer Center
    Philadelphia, Pennsylvania 19104, United States
  • Local Institution - 034
    Fort Sam Houston, Texas 78234, United States
  • Local Institution - 079
    Houston, Texas 77058, United States
  • Local Institution - 196
    Houston, Texas 77089, United States
  • Gulf Coast Research Group LLC
    Houston, Texas 77098, United States
  • Accurate Clinical Research Inc
    Pasadena, Texas 77505, United States
  • Local Institution - 071
    Richardson, Texas 75082, United States
  • Local Institution - 178
    San Antonio, Texas 78229, United States
  • Local Institution - 181
    Temple, Texas 76508, United States
  • Local Institution - 292
    Riverton, Utah 84065, United States
  • Local Institution - 030
    Lynchburg, Virginia 24502, United States
  • The Gastroenterology Group
    Reston, Virginia 20191, United States
  • Local Institution - 072
    Richmond, Virginia 23249, United States
  • Local Institution - 172
    Roanoke, Virginia 24016, United States
  • Local Institution - 089
    La Crosse, Wisconsin 54601, United States
  • Local Institution - 309
    Liverpool, New South Wales 2170, Australia
  • Local Institution - 318
    New Lambton Heights, New South Wales 2305, Australia
  • Local Institution - 328
    Herston, Queensland 4029, Australia
  • Local Institution - 313
    Maroorchydore, Queensland 4558, Australia
  • Local Institution - 321
    North Mackay, Queensland 4740, Australia
  • Local Institution - 312
    South Brisbane, Queensland 4101, Australia
  • Local Institution - 307
    Bedford Park, South Australia 5042, Australia
  • Local Institution - 326
    Elizabeth Vale, South Australia 05112, Australia
  • Local Institution - 317
    Clayton, Victoria 3168, Australia
  • Local Institution - 305
    Fitzroy, Victoria 3065, Australia
  • Local Institution - 329
    Geelong, Victoria 3220, Australia
  • Local Institution - 327
    Melbourne, Victoria 3004, Australia
  • Local Institution - 315
    Subiaco, Western Australia 6008, Australia
  • Local Institution - 726
    Innsbruck, 6020, Austria
  • Local Institution - 727
    St Polten, 3100, Austria
  • Local Institution - 336
    Vienna, 1020, Austria
  • Local Institution - 725
    Vienna, 1090, Austria
  • Local Institution - 753
    Ruse, 7002, Bulgaria
  • Local Institution - 750
    Sofia, 1407, Bulgaria

Showing the first 100 of 368 sites across 31 countries.

08

References and documents

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. PubMed 36208720 ↗

Study documents

  • Protocol and statistical analysis plan · Jun 14, 2021

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03440385
Lead sponsor
Celgene
Responsible party
Sponsor
First posted
Feb 22, 2018
Start date
Mar 7, 2018
Primary completion
Nov 21, 2023
Completion
Nov 21, 2023
Results posted
Dec 5, 2024
Last update
Dec 5, 2024

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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