A Study to Evaluate the Efficacy, Safety, and Drug Levels of Oral Ozanimod in Pediatric Participants With Moderately to Severely Active Crohn's Disease With an Inadequate Response to Conventional Therapy

A Phase 2/3, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Oral Ozanimod (RPC1063) in Pediatric Participants With Moderately to Severely Active Crohn's Disease With an Inadequate Response to Conventional Therapy

The purpose of this study is to evaluate the efficacy, safety, drug levels, and drug effects of ozanimod in pediatric participants with moderately to severely active Crohn's Disease.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Ozanimod

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Joonladup, Western Australia, Australia, 6027
      • Local Institution - 0045
• Belgium
  • Brussel, Belgium, 1090
    • Local Institution - 0047
  • Bruxelles, Belgium, 1200
    • Local Institution - 0055
  • BRU
    • Brussel, BRU, Belgium, 1020
      • Local Institution - 0058
  • VBR
    • Leuven, VBR, Belgium, 3000
      • Local Institution - 0023
  • WLG
    • Liege, WLG, Belgium, 4000
      • Local Institution - 0062
    • Liège, WLG, Belgium, 4000
      • Local Institution - 0048
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • Local Institution - 0014
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Local Institution - 0001
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Local Institution - 0054
• France
  • Bron, France, 69500
    • Local Institution - 0066
  • Caen, France, 14033
    • Local Institution - 0065
  • Paris, France, 75015
    • Local Institution - 0072
  • Toulouse, France, 31059
    • Local Institution - 0063
• Germany
  • SN
    • Dresden, SN, Germany, 01307
      • Local Institution - 0057
    • Leipzig, SN, Germany, 04103
      • Local Institution - 0067
• Hungary
  • Miskolc, Hungary, 3526
    • Local Institution - 0015
  • Szeged, Hungary, 6720
    • Local Institution - 0026
• Poland
  • Lodz, Poland, 91-738
    • Local Institution - 0061
  • Warsaw, Poland, 04-746
    • Local Institution - 0033
  • Warszawa, Poland, 00-635
    • Local Institution - 0031
  • MZ
    • Warszawa, MZ, Poland, 00-728
      • Local Institution - 0007
  • PK
    • Rzeszow, PK, Poland, 35-302
      • Local Institution - 0052
• Spain
  • Badalona, Spain, 08916
    • Local Institution - 0030
  • Barcelone, Spain, 08035
    • Local Institution - 0035
  • Madrid, Spain, 28009
    • Local Institution - 0017
  • B
    • Barcelona, B, Spain, 8950
      • Local Institution - 0025
• United States
  • California
    • Garden Grove, California, United States, 92845-2032
      • Local Institution - 0010
    • Los Angeles, California, United States, 90027-6062
      • Local Institution - 0028
    • Sacramento, California, United States, 95817-2207
      • Local Institution - 0002
    • San Francisco, California, United States, 94158
      • Local Institution - 0009
  • Connecticut
    • Hartford, Connecticut, United States, 06106-3322
      • Local Institution - 0011
  • Florida
    • Orlando, Florida, United States, 32803-1469
      • Local Institution - 0044
    • Orlando, Florida, United States, 32806
      • Local Institution - 0037
  • Georgia
    • Atlanta, Georgia, United States, 30302
      • Local Institution - 0053
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5109
      • Local Institution - 0059
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Local Institution - 0038
  • Michigan
    • Detroit, Michigan, United States, 48201-2196
      • Local Institution - 0006
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Local Institution - 0003
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1002
      • Local Institution - 0016
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-1000
      • Local Institution - 0071
  • New York
    • New York, New York, United States, 10032
      • Local Institution - 0060
  • Texas
    • Fort Worth, Texas, United States, 76104-2710
      • Local Institution - 0075
    • Houston, Texas, United States, 77030-2316
      • Local Institution - 0070
  • Washington
    • Seattle, Washington, United States, 98105-3901
      • Local Institution - 0008
    • Tacoma, Washington, United States, 98405-3720
      • Local Institution - 0040

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have a Pediatric Crohn's Disease Activity Index (PCDAI) score ≥ 30 and a Simple Endoscopic Score for Crohn's Disease (SES-CD) score ≥ 6 (or SES-CD ≥ 4 in participants with isolated ileal disease)

• Participant has an inadequate response, intolerance, or loss of response to at least 1 of the following treatments for Crohn's Disease (CD):

  i) corticosteroids ii) immunomodulators iii) biologic therapy iv) other systemic immunomodulatory therapies for CD

Exclusion Criteria:

• Participant is likely to require, in the physician's judgment, bowel resection within 12 weeks of entry into the study
• Participant has current stoma, ileal-anal pouch anastomosis, fistula that is likely to require, in the physician's judgment, surgical or medical intervention within 12 weeks of entry into the study or need for ileostomy or colostomy
• Participant has extensive small bowel resection (> 100 cm) or known diagnosis of short bowel syndrome or participant requires total parenteral nutrition

Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ozanimod Dose Level 1	Drug: Ozanimod; Specific dose on specific days; Other Names: BMS-986374; RPC1063
Experimental: Ozanimod Dose Level 2	Drug: Ozanimod; Specific dose on specific days; Other Names: BMS-986374; RPC1063

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve Pediatric Crohn's Disease Activity Index (PCDAI) Score < 10 at Week 64	The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD. The PCDAI consists of the following 11 variables: Abdominal pain, stools per day, wellbeing, weight, height velocity, abdominal tenderness, peri-rectal disease, extra-intestinal manifestation, hematocrit, erythrocyte sedimentation rate and albumin. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. The PCDAI score is average of 11 variables scoring range of 0 to 100. Mild disease corresponds to scores of 11 to 30; moderate to severe disease corresponds to scores > 30. Remission (no disease activity) is defined as a PCDAI score < 10.	Week 64
Percentage of Participants Achieving Simple Endoscopic Score for Crohn's Disease (SES-CD) ≤ 2 or SES-CD ≤ 4 Points With no SES-CD Subscore > 1 Point at Week 64	SES-CD assesses the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right colon, transverse colon, left (descending and sigmoid) colon, and rectum, and is scored on a scale of severity 0 (Normal) to 3 (High). Sub-scores for each segment will be derived by adding component scores within segments. Total SES-CD score is the sum of the sub-scores across the five segments. The sum of each component across all segments ranges from 0 to 15, except for the presence of narrowing where it varies from 0 to 11. The range of the overall SES-CD score is 0-56, with larger scores indicating greater severity of disease.	Week 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve Pediatric Crohn's Disease Activity Index (PCDAI) < 10 at Week 12 Based on Data as Observed	The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD. The PCDAI consists of the following 11 variables: Abdominal pain, stools per day, wellbeing, weight, height velocity, abdominal tenderness, peri-rectal disease, extra-intestinal manifestation, hematocrit, erythrocyte sedimentation rate and albumin. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. The PCDAI score is average of 11 variables scoring range of 0 to 100. Mild disease corresponds to scores of 11 to 30; moderate to severe disease corresponds to scores > 30. Remission (no disease activity) is defined as a PCDAI score < 10.	Week 12
Percentage of Participants Who Achieve Simple Endoscopic Score for Crohn's Disease (SES-CD) Decrease From Baseline of ≥ 50% (ER-50) at Week 64	SES-CD assesses the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right colon, transverse colon, left (descending and sigmoid) colon, and rectum, and is scored on a scale of severity 0 (Normal) to 3 (High). Sub-scores for each segment will be derived by adding component scores within segments. Total SES-CD score is the sum of the sub-scores across the five segments. The sum of each component across all segments ranges from 0 to 15, except for the presence of narrowing where it varies from 0 to 11. The range of the overall SES-CD score is 0-56, with larger scores indicating greater severity of disease.	Week 64
Percentage of Participants Who Achieve Simple Endoscopic Score for Crohn's Disease (SES-CD) Decrease From Baseline of ≥ 50% (ER-50) at Week 12 Based on Data as Observed	SES-CD assesses the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right colon, transverse colon, left (descending and sigmoid) colon, and rectum, and is scored on a scale of severity 0 (Normal) to 3 (High). Sub-scores for each segment will be derived by adding component scores within segments. Total SES-CD score is the sum of the sub-scores across the five segments. The sum of each component across all segments ranges from 0 to 15, except for the presence of narrowing where it varies from 0 to 11. The range of the overall SES-CD score is 0-56, with larger scores indicating greater severity of disease.	Week 12
Percentage of Participants Who Achieve Reduction in Pediatric Crohn's Disease Activity Index (PCDAI) Score ≥ 12.5 and a Total PCDAI Score of < 30 Points at Week 64	The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD. The PCDAI consists of the following 11 variables: Abdominal pain, stools per day, wellbeing, weight, height velocity, abdominal tenderness, peri-rectal disease, extra-intestinal manifestation, hematocrit, erythrocyte sedimentation rate and albumin. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. The PCDAI score is average of 11 variables scoring range of 0 to 100. Mild disease corresponds to scores of 11 to 30; moderate to severe disease corresponds to scores > 30. Remission (no disease activity) is defined as a PCDAI score < 10.	Week 64
Percentage of Participants Who Achieve Reduction in Pediatric Crohn's Disease Activity Index (PCDAI) Score ≥ 12.5 and a Total PCDAI Score of < 30 Points at Week 12 Based on Data as Observed	The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD. The PCDAI consists of the following 11 variables: Abdominal pain, stools per day, wellbeing, weight, height velocity, abdominal tenderness, peri-rectal disease, extra-intestinal manifestation, hematocrit, erythrocyte sedimentation rate and albumin. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. The PCDAI score is average of 11 variables scoring range of 0 to 100. Mild disease corresponds to scores of 11 to 30; moderate to severe disease corresponds to scores > 30. Remission (no disease activity) is defined as a PCDAI score < 10.	Week 12
Percentage of Adolescents Who Achieve an Average Daily Abdominal Pain Score ≤ 1 Point and an Average Daily Stool Frequency ≤ 3 Points With Abdominal Pain and Stool Frequency no Worse Than Baseline at Week 12 Based on Data as Observed	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.	Week 12
Percentage of Adolescents Who Achieve an Average Daily Abdominal Pain Score ≤ 1 Point and an Average Daily Stool Frequency ≤ 3 Points With Abdominal Pain and Stool Frequency no Worse Than Baseline at Week 64	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.	Week 64
Change From Baseline in Stool Frequency (SF) Score at Week 64	SF was defined number of liquid or soft stools per day.	Baseline and Week 64
Change From Baseline in Abdominal Pain (AP) Score at Week 64	Participants entered Reponses in diaries daily. The 7 days entries prior to visit were considered for calculating average AP score. The AP score was graded on severity of 0 (none) to 3 (severe) scale.	Baseline and Week 64
Percentage of Adolescents Who Achieve Crohn's Disease Activity Index (CDAI) Score < 150 at Week 12 Based on Data as Observed	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.	Week 12
Percentage of Adolescents Who Achieve Crohn's Disease Activity Index (CDAI) Score < 150 at Week 64	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.	Week 64
Percentage of Adolescents Who Achieve Crohn's Disease Activity Index (CDAI) Reduction From Baseline of ≥ 100 Points or CDAI Score < 150 at Week 64	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.	Week 64
Percentage of Adolescents Who Achieve Crohn's Disease Activity Index (CDAI) Reduction From Baseline of ≥ 100 Points or CDAI Score < 150 at Week 12 Based on Data as Observed	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.	Week 12
Percentage of Participants Who Achieve a Pediatric Crohn's Disease Activity Index (PCDAI) Score < 10 at Week 64 While Remaining Corticosteroid Free in the Prior 12 Weeks	The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD. The PCDAI consists of the following 11 variables: Abdominal pain, stools per day, wellbeing, weight, height velocity, abdominal tenderness, peri-rectal disease, extra-intestinal manifestation, hematocrit, erythrocyte sedimentation rate and albumin. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. The PCDAI score is average of 11 variables scoring range of 0 to 100. Mild disease corresponds to scores of 11 to 30; moderate to severe disease corresponds to scores > 30. Remission (no disease activity) is defined as a PCDAI score < 10.	Week 64
Percentage of Adolescents Who Achieve a Pediatric Crohn's Disease Activity Index (PCDAI) Score < 10 at Week 64 While Remaining Corticosteroid Free in the Prior 12 Weeks	The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD. The PCDAI consists of the following 11 variables: Abdominal pain, stools per day, wellbeing, weight, height velocity, abdominal tenderness, peri-rectal disease, extra-intestinal manifestation, hematocrit, erythrocyte sedimentation rate and albumin. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. The PCDAI score is average of 11 variables scoring range of 0 to 100. Mild disease corresponds to scores of 11 to 30; moderate to severe disease corresponds to scores > 30. Remission (no disease activity) is defined as a PCDAI score < 10.	Week 64
Percentage of Participants Who Achieve a Crohn's Disease Activity Index (CDAI) Score < 150 at Week 64 While Remaining Corticosteroid Free in the Prior 12 Weeks	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.	Week 64
Percentage of Participants Achieving Simple Endoscopic Score for Crohn's Disease (SES-CD) ≤ 2 or SES-CD ≤ 4 Points With no SES-CD Subscore > 1 Point at Week 12 Based on Data as Observed	SES-CD assesses the degree of inflammation on the basis of 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right colon, transverse colon, left (descending and sigmoid) colon, and rectum, and is scored on a scale of severity 0 (Normal) to 3 (High). Sub-scores for each segment will be derived by adding component scores within segments. Total SES-CD score is the sum of the sub-scores across the five segments. The sum of each component across all segments ranges from 0 to 15, except for the presence of narrowing where it varies from 0 to 11. The range of the overall SES-CD score is 0-56, with larger scores indicating greater severity of disease.	Week 12
Steady State Systemic Exposures of Ozanimod at Week 20 and Throughout the Study	Blood samples were collected to assess steady state exposure of ozanimod.	Week 20 and up to end of study (Week 64)
Absolute Lymphocyte Count at Week 12 Based on Data as Observed	Blood samples were collected to assess lymphocyte count.	Baseline (Day 1) and Week 12
Absolute Lymphocyte Count at Week 64	Blood samples were collected to assess lymphocyte count.	Week 64
Number of Participants With Adverse Events	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Serious Adverse Events (SAEs) is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect.	From first dose (Day 1) and up to Week 12

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2023
• Primary Completion (Actual): September 13, 2024
• Study Completion (Actual): September 13, 2024

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Sphingosine 1 Phosphate Receptor Modulators; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Ozanimod
• Other Study ID Numbers: IM047-023; 2021-005019-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No