Crohn's Disease
Conditions
Brief summary
The purpose is to determine whether RPC1063 is effective in the treatment of Crohn's disease.
Detailed description
This open-label trial is composed of two periods: Induction and Extension. All eligible patients will be enrolled into the 12-Week Induction period and receive study medication. Patients who complete the Induction period may then be eligible to enter the 100-Week Extension period where they will continue to receive study medication.
Interventions
DRUGRPC1063
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Crohn's disease (CD) confirmed by endoscopy and histology * Active disease as evaluated by Crohn's Disease Activity Index Score and Simple Endoscopic Score for CD * Inadequate response to aminosalicylates, corticosteroids, immunomodulators or biologic therapy Key
Exclusion criteria
* Diagnosis of ulcerative colitis or indeterminate colitis * Known strictures/stenosis leading to symptoms of obstruction * Current stoma or need for ileostomy or colostomy * Clinically relevant cardiovascular conditions or other relevant diseases that could impact the implementation or interpretation of the trial, or put the patient at risk * History of uveitis or known macular edema * History of colonic dysplasia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Simple Endoscopic Score for Crohn's Disease (SES-CD) (Paired Segments) From Baseline at Week 12 as Determined by a Blinded Central Reader. | Baseline to Week 12 | The simple endoscopy score (SES-CD) assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | From the first day of ozanimod up to 90 days after the last dose of ozanimod; mean duration of exposure of study drug was 1.305 years | A TEAE = any event with an onset date on or after the first dose date, or any ongoing event on the first dose date that worsens in severity or after the first dose date and until 90 days following the last dose of study drug treatment. An AE = untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which that does not necessarily have a causal relationship with the investigational treatment. An AE can be any unfavorable or unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not considered related to the investigational medicinal product. A serious AE (experience) or reaction is any untoward medical occurrence that at any dose * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity, or * Is a congenital abnormality/birth defect |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Clinical Response Based on Crohn's Disease Activity Index (CDAI) at Week 12 | Week 12 | Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 12 | Week 12 | The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency (SF) and abdominal pain (AP) (rated on a scale of 0-3) assessed for 7 days. Clinical Remission (SF and AP remission) was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 12 | Week 12 | Clinical response based on PRO2 was defined as PRO2 decrease of ≥50% from baseline. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12 (Paired Segments) | Week 12 | Endoscopic remission is defined as SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score \>1point. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved an Endoscopic Response-50 (Paired Segment) Based on Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12 | Week 12 | Endoscopic Response is defined as a SES-CD decrease from baseline of ≥ 50%. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Change in Roberts Intestinal Histopathology Index From Baseline (Paired Segments) at Week 12 | Week 12 | Changes in intestinal mucosa histopathologic features and disease activity were assessed by blinded pathologists. Robarts Histopathology Index (RHI) had a maximum total score of 165, with higher scores indicating more severe histological disease. Baseline was defined as the last non-missing record on or before the first dose of study drug. |
| Improvement in Perianal and Enterocutaneous Fistulas | Week 12 | The assessment is based on two parameters: whether the fistula is draining and whether it's open or closed. This is assessment was only on participants that had a fistula at baseline. |
| Percentage of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 - Observed Cases | Week 52 | Endoscopic remission is defined as SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score \>1point. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved an Endoscopic Response-50 Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 | Week 52 | Endoscopic Response is defined as a SES-CD decrease from baseline of ≥ 50%. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.. |
| Percentage of Participants Who Achieved Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 52 | Week 52 | Clinical Remission is defined as a CDAI score of \< 150. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Week 52 | Week 52 | Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 52 | Week 52 | Clinical Remission is defined as the participants with the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. |
| Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 52 | Week 52 | Clinical response based on PRO2 was defined as PRO2 decrease of ≥50% from baseline. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Change in the Crohn's Disease Activity Index (CDAI) Score From Baseline at Week 12 | Baseline to Week 12 | The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. Baseline was defined as the last non-missing record on or before the first dose of study drug. |
| Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Weeks 4 and 8 | Weeks 4 and 8 | Clinical Remission is defined as a CDAI score of \< 150. The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Weeks 4 and 8 | Weeks 4 and 8 | Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% CI was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Weeks 4 and 8 | Weeks 4 and 8 | The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency (SF) and abdominal pain (AP) (rated on a scale of 0-3) assessed for 7 days. Clinical Remission (SF and AP remission) was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures at Weeks 4 and 8 | Weeks 4 and Week 8 | Clinical response based on PRO2 was defined as PRO2 decrease of ≥50%. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants With RHI Healing at Week 52 | Week 52 | Changes from baseline in intestinal mucosa histopathologic features and disease activity were assessed by blinded pathologists. Robarts Histopathology Index (RHI) had a maximum total score of 165, with higher scores indicating more severe histological disease. Baseline was defined as the last non-missing record on or before the first dose of study drug. The Robarts Histopathology Index (RHI) is a recently validated instrument that measures histological disease activity in ulcerative colitis. RHI Mucosal Healing was defined as a composite endpoint of being a responder for endoscopic remission and RHI remission. |
| Change in Fecal Calprotectin (Observed Cases) at Weeks 12 and 52 | Baseline to Weeks 12 and Week 52 | Change in fecal calprotectin (observed cases) determined by comparing measurements at weeks 12 and 52 to baseline measurement. |
| Change in Serum C-Reactive Protein (CRP) Levels From Baseline (Observed Cases) at Weeks 12 and 52 | Baseline to Weeks 12 and 52 | Change in Serum C-Reactive Protein was determined by comparing to baseline. |
| Changes in Biomarkers: Percentage of Participants With CRP Response-10 - Non-responder Imputation | Week 12, Week 52 | The percentage of participants with a CRP Response-10 was assessed. CRP Response-10 is defined as C-reactive protein \< 10 mg/L. |
| Changes in Biomarkers: Percentage of Participants With FCP Response-250 - Non-responder Imputation | Week 12, Week 52 | The percentage of participants with a FCP Response-250 was assessed. FCP Response-250 is defined as Fecal calprotectin \< 250 ug/g. |
| Improvement in Perianal and Enterocutaneous Fistulas in Participants With Fistula's From Baseline at Weeks 4 and 8 | Baseline to Week 4 and 8 | The assessment is based on two parameters: whether the fistula is draining and whether it's open or closed. This is assessment was only on participants that had a fistula at baseline. |
| Pharmacokinetic Plasma Concentration of Ozanimod | From Day 1 to Week 52 | Summary of concentrations of Ozanimod in RPC01-2201 by scheduled visit. |
| PK Plasma Concentration of Active Metabolite CC-112273 | From Day 1 to Week 52 | Summary of concentrations of CC-112273 in RPC01-2201 by scheduled visit. |
| Change From Baseline in Absolute Lymphocyte Count (ALC) Derived From Hematology Laboratory Results at Weeks 4, 8 and 12 | Baseline up to Weeks 4, 8 and 12 | Change in Absolute Lymphocyte Count (ALC) from baseline was determined by comparied to baseline. |
| Percentage of Participants in Clinical Remission Based on CDAI and PRO2 Definitions Who Were Off Corticosteroids at Week 52 of Those on Corticosteroids | Week 52 | Clinical Remission is defined as CDAI score of \< 150. The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI uses a questionnaire with responses scored numerically and weighted. The weighted sum of the 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, general well-being for 7 days, presence of complications, taking diarrhea medication, abdominal mass, hematocrit and percentage deviation from standard weight. The typical range of CDAI score is 0 to \> 600. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
| Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 12 | Week 12 | Clinical Remission is defined as a CDAI score of \< 150. The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method. |
Countries
Canada, Hungary, Poland, Ukraine, United States
Participant flow
Recruitment details
Sixty-nine adult participants were enrolled from 28 sites located in Europe and North America.
Pre-assignment details
Eligible participants must have had a Crohn's Disease Activity Index (CDAI) score of 220 to 450 inclusive with an Simple Endoscopic Score for Crohn's Disease (SES-CD) score of ≥ 6 and an average daily stool score ≥ 4 points and/or an average daily abdominal pain score of ≥ 2 points.
Participants by arm
| Arm | Count |
|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg Participants received ozanimod 1 mg capsules daily for the first 12 weeks of the induction period (an initial 7-day dose escalation regimen that consisted of 4 days of ozanimod HCl 0.25 mg (equivalent to ozanimod 0.23 mg) daily followed by 3 days of ozanimod HCl 0.5 mg (equivalent to ozanimod 0.46 mg) daily, with the final dose of ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) daily dose reached on Day 8. Participants who completed the induction period had the opportunity at Week 12 to continue to receive ozanimod 1 mg capsules daily during the extension period up to an additional 148 weeks, provided that the investigator determined that the participant should continue. Participants in the extension period continued to receive ozanimod 1 mg capsules daily through Week 160. Participants who completed the Week 160 visit had the option to continue open-label ozanimod 1 mg capsules by immediately entering the open-label extension Phase 3 Crohn's Disease Study RPC01-3204 (NCT03467958). | 69 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Period: Week 12 up to Week 160 | Adverse Event | 5 |
| Extension Period: Week 12 up to Week 160 | Lack of Efficacy | 19 |
| Extension Period: Week 12 up to Week 160 | Physician Decision | 2 |
| Extension Period: Week 12 up to Week 160 | Pregnancy | 1 |
| Extension Period: Week 12 up to Week 160 | Withdrawal by Subject | 11 |
| Induction Period: Week 0 to 12 | Adverse Event | 4 |
| Induction Period: Week 0 to 12 | Lack of Efficacy | 4 |
| Induction Period: Week 0 to 12 | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Ozanimod Hydrochloride (HCl) 1 mg |
|---|---|
| Age, Continuous | 37.7 Years STANDARD_DEVIATION 11.97 |
| C-reactive Protein (mg/L) at Baseline | 18.2 (mg/L) STANDARD_DEVIATION 25.36 |
| Crohn's Disease Activity Index (CDAI) Score at Baseline | 322.8 Units on a Scale STANDARD_DEVIATION 59.19 |
| Daily Abdominal Pain Score at Baseline | 2.05 Units on a Scale STANDARD_DEVIATION 0.526 |
| Daily Stool Frequency (SF) at Baseline | 6.15 Stools/day STANDARD_DEVIATION 2.792 |
| Disease Location Colon Only | 26 Participants |
| Disease Location Ileocolonic (Ileum and Colon) | 32 Participants |
| Disease Location Ileum Only | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fecal Calprotectin at Baseline | 1158.17 μg/g STANDARD_DEVIATION 1231.267 |
| Prior Corticosteroid Use No Prior Use of Corticosteroids | 7 Participants |
| Prior Corticosteroid Use Prior Use of Corticosteroids | 62 Participants |
| Prior Use of Immunomodulator No Prior Use of Immunomodulator | 31 Participants |
| Prior Use of Immunomodulator Prior Use of Immunomodulator | 38 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 60 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 33 Participants |
| Simple Endoscopic Score for Crohn's Disease (SES-CD) at Baseline | 13.28 Units on a Scale STANDARD_DEVIATION 6.584 |
| Years Since Crohn's Disease Diagnosis | 8.9 Years STANDARD_DEVIATION 8.53 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 69 |
| other Total, other adverse events | 47 / 69 |
| serious Total, serious adverse events | 18 / 69 |
Outcome results
Primary
Change in Simple Endoscopic Score for Crohn's Disease (SES-CD) (Paired Segments) From Baseline at Week 12 as Determined by a Blinded Central Reader.
The simple endoscopy score (SES-CD) assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease.
Time frame: Baseline to Week 12
Population: The intent to treat population = all enrolled participants who received at least one dose of ozanimod. For paired segment scores, any missing segment scores, were imputed by non-missing score used in previous visit. Analysis for change from baseline includes those with data available at baseline and visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Change in Simple Endoscopic Score for Crohn's Disease (SES-CD) (Paired Segments) From Baseline at Week 12 as Determined by a Blinded Central Reader. | -2.3 Units on a Scale | Standard Deviation 6.2 |
Secondary
The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period
A TEAE = any event with an onset date on or after the first dose date, or any ongoing event on the first dose date that worsens in severity or after the first dose date and until 90 days following the last dose of study drug treatment. An AE = untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which that does not necessarily have a causal relationship with the investigational treatment. An AE can be any unfavorable or unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not considered related to the investigational medicinal product. A serious AE (experience) or reaction is any untoward medical occurrence that at any dose * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity, or * Is a congenital abnormality/birth defect
Time frame: From the first day of ozanimod up to 90 days after the last dose of ozanimod; mean duration of exposure of study drug was 1.305 years
Population: The Safety population included all enrolled participants who received at least one dose of ozanimod.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 TEAE | 59 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 Moderate or Severe TEAE | 43 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 Severe TEAE | 15 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 Possible, Probable or Related TEAE | 24 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 Related TEAE | 7 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 Serious TEAE | 18 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 Possible, Probable or Related Serious TEAE | 4 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 Related Serious TEAE | 1 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 TEAE Leading to Discontinuation of Ozanimod | 11 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ≥ 1 TEAE Leading to Study Withdrawal | 11 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | Death | 1 Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | Death Possible, Probable or Related to Ozanimod | 1 Participants |
Other Pre-specified
Change From Baseline in Absolute Lymphocyte Count (ALC) Derived From Hematology Laboratory Results at Weeks 4, 8 and 12
Change in Absolute Lymphocyte Count (ALC) from baseline was determined by comparied to baseline.
Time frame: Baseline up to Weeks 4, 8 and 12
Population: The safety population included all enrolled participants who received at least one dose of ozanimod.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Change From Baseline in Absolute Lymphocyte Count (ALC) Derived From Hematology Laboratory Results at Weeks 4, 8 and 12 | Week 4 | -0.946 10 ^9 cells/L | Standard Deviation 0.783 |
| Ozanimod Hydrochloride (HCl) 1 mg | Change From Baseline in Absolute Lymphocyte Count (ALC) Derived From Hematology Laboratory Results at Weeks 4, 8 and 12 | Week 8 | -1.086 10 ^9 cells/L | Standard Deviation 0.778 |
| Ozanimod Hydrochloride (HCl) 1 mg | Change From Baseline in Absolute Lymphocyte Count (ALC) Derived From Hematology Laboratory Results at Weeks 4, 8 and 12 | Week 12 | -1.092 10 ^9 cells/L | Standard Deviation 0.783 |
Other Pre-specified
Change in Fecal Calprotectin (Observed Cases) at Weeks 12 and 52
Change in fecal calprotectin (observed cases) determined by comparing measurements at weeks 12 and 52 to baseline measurement.
Time frame: Baseline to Weeks 12 and Week 52
Population: The intent to treat population (ITT) includes all enrolled participants who received at least one dose of ozanimod. Analysis for change from baseline includes participants with data available at baseline and visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Change in Fecal Calprotectin (Observed Cases) at Weeks 12 and 52 | Week 12 | -41.0 μg/g |
| Ozanimod Hydrochloride (HCl) 1 mg | Change in Fecal Calprotectin (Observed Cases) at Weeks 12 and 52 | Week 52 | -103.3 μg/g |
Other Pre-specified
Change in Roberts Intestinal Histopathology Index From Baseline (Paired Segments) at Week 12
Changes in intestinal mucosa histopathologic features and disease activity were assessed by blinded pathologists. Robarts Histopathology Index (RHI) had a maximum total score of 165, with higher scores indicating more severe histological disease. Baseline was defined as the last non-missing record on or before the first dose of study drug.
Time frame: Week 12
Population: The ITT population = all enrolled participants who received at least one dose of ozanimod. For paired segment analysis, any missing segment scores in the presence of at least 1 non-missing segmental SES-CD score were imputed by non-missing score used in the previous visit. Analysis includes participants with data available at baseline and visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Change in Roberts Intestinal Histopathology Index From Baseline (Paired Segments) at Week 12 | -10.2 Units on a Scale | Standard Deviation 25.83 |
Other Pre-specified
Change in Serum C-Reactive Protein (CRP) Levels From Baseline (Observed Cases) at Weeks 12 and 52
Change in Serum C-Reactive Protein was determined by comparing to baseline.
Time frame: Baseline to Weeks 12 and 52
Population: The intent to treat population (ITT) includes all enrolled participants who received at least one dose of ozanimod. Analysis for change from baseline includes participants with data available at baseline and visit.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Change in Serum C-Reactive Protein (CRP) Levels From Baseline (Observed Cases) at Weeks 12 and 52 | Week 52 | -0.5 mg/L |
| Ozanimod Hydrochloride (HCl) 1 mg | Change in Serum C-Reactive Protein (CRP) Levels From Baseline (Observed Cases) at Weeks 12 and 52 | Week 12 | 1.0 mg/L |
Other Pre-specified
Change in the Crohn's Disease Activity Index (CDAI) Score From Baseline at Week 12
The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. Baseline was defined as the last non-missing record on or before the first dose of study drug.
Time frame: Baseline to Week 12
Population: The ITT included all enrolled participants and received at least one dose of ozanimod. Analysis for change from baseline includes participants with data available at baseline and visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Change in the Crohn's Disease Activity Index (CDAI) Score From Baseline at Week 12 | -141.5 Units on a Scale | Standard Deviation 99.42 |
Other Pre-specified
Changes in Biomarkers: Percentage of Participants With CRP Response-10 - Non-responder Imputation
The percentage of participants with a CRP Response-10 was assessed. CRP Response-10 is defined as C-reactive protein \< 10 mg/L.
Time frame: Week 12, Week 52
Population: The intent to treat population = all enrolled participants who received at least one dose of ozanimod.~If any scores are missing then non-responder imputation is applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Changes in Biomarkers: Percentage of Participants With CRP Response-10 - Non-responder Imputation | Week 12 | 39.1 Percentage of participants |
| Ozanimod Hydrochloride (HCl) 1 mg | Changes in Biomarkers: Percentage of Participants With CRP Response-10 - Non-responder Imputation | Week 52 | 23.2 Percentage of participants |
Other Pre-specified
Changes in Biomarkers: Percentage of Participants With FCP Response-250 - Non-responder Imputation
The percentage of participants with a FCP Response-250 was assessed. FCP Response-250 is defined as Fecal calprotectin \< 250 ug/g.
Time frame: Week 12, Week 52
Population: The intent to treat population = all enrolled participants who received at least one dose of ozanimod.~If any Fecal Calprotectin are missing then non-responder imputation is applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Changes in Biomarkers: Percentage of Participants With FCP Response-250 - Non-responder Imputation | Week 12 | 30.4 Percentage of participants |
| Ozanimod Hydrochloride (HCl) 1 mg | Changes in Biomarkers: Percentage of Participants With FCP Response-250 - Non-responder Imputation | Week 52 | 11.6 Percentage of participants |
Other Pre-specified
Improvement in Perianal and Enterocutaneous Fistulas
The assessment is based on two parameters: whether the fistula is draining and whether it's open or closed. This is assessment was only on participants that had a fistula at baseline.
Time frame: Week 12
Population: This endpoint was omitted because there were too few study participants with perianal or enterocutaneous fistulas at baseline to allow for meaningful evaluation. No analysis performed.
Other Pre-specified
Improvement in Perianal and Enterocutaneous Fistulas in Participants With Fistula's From Baseline at Weeks 4 and 8
The assessment is based on two parameters: whether the fistula is draining and whether it's open or closed. This is assessment was only on participants that had a fistula at baseline.
Time frame: Baseline to Week 4 and 8
Population: This endpoint was omitted because there were too few study participants with perianal or enterocutaneous fistulas at baseline to allow for meaningful evaluation. No analysis performed.
Other Pre-specified
Percentage of Participants in Clinical Remission Based on CDAI and PRO2 Definitions Who Were Off Corticosteroids at Week 52 of Those on Corticosteroids
Clinical Remission is defined as CDAI score of \< 150. The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI uses a questionnaire with responses scored numerically and weighted. The weighted sum of the 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, general well-being for 7 days, presence of complications, taking diarrhea medication, abdominal mass, hematocrit and percentage deviation from standard weight. The typical range of CDAI score is 0 to \> 600. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 52
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. Participants who were taking corticosteroids at baseline. Observed cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants in Clinical Remission Based on CDAI and PRO2 Definitions Who Were Off Corticosteroids at Week 52 of Those on Corticosteroids | 18.8 Percentage of Participants |
Other Pre-specified
Percentage of Participants of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12 (Paired Segments)
Endoscopic remission is defined as SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score \>1point. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 12
Population: The ITT = all enrolled participants who received at least one dose of ozanimod. For paired segments analysis, any missing segment scores in the presence of at least 1 non-missing segmental SES-CD score were imputed by non-missing score used in the previous visit. If post-baseline SES-CD score was missing, then NRI was applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12 (Paired Segments) | 10.1 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Week 52
Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 52
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. Observed Cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Week 52 | 93.8 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Weeks 4 and 8
Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% CI was created using the Clopper-Pearson Exact Method.
Time frame: Weeks 4 and 8
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. If CDAI score was missing, then non-responder imputation was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Weeks 4 and 8 | Weeks 4 | 37.7 Percentage of Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Weeks 4 and 8 | Weeks 8 | 52.2 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved a Clinical Response Based on Crohn's Disease Activity Index (CDAI) at Week 12
Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 12
Population: The ITT included all enrolled participants and received at least one dose of ozanimod. If CDAI score was missing, then non-responder imputation (NRI) was applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on Crohn's Disease Activity Index (CDAI) at Week 12 | 50.7 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures at Weeks 4 and 8
Clinical response based on PRO2 was defined as PRO2 decrease of ≥50%. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Weeks 4 and Week 8
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. If PRO2 CD score is missing, then Non-responder imputation (NRI) was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures at Weeks 4 and 8 | Week 4 | 20.3 Percentage of Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures at Weeks 4 and 8 | Week 8 | 33.3 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 12
Clinical response based on PRO2 was defined as PRO2 decrease of ≥50% from baseline. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 12
Population: The ITT included all enrolled participants and received at least one dose of ozanimod. If PRO2 CD score was missing, then non-responder imputation (NRI) was applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 12 | 29.0 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 52
Clinical response based on PRO2 was defined as PRO2 decrease of ≥50% from baseline. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 52
Population: The ITT included all enrolled participants and received at least one dose of ozanimod. Observed Cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 52 | 65.6 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved an Endoscopic Response-50 Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52
Endoscopic Response is defined as a SES-CD decrease from baseline of ≥ 50%. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method..
Time frame: Week 52
Population: The intent to treat population (ITT) = all enrolled participants who received at least one dose of ozanimod. For Robarts Observed Score, the SES-CD score is determined based on all available segments at a given visit without adjusting for the segments available at baseline.Observed cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved an Endoscopic Response-50 Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 | 30.0 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved an Endoscopic Response-50 (Paired Segment) Based on Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12
Endoscopic Response is defined as a SES-CD decrease from baseline of ≥ 50%. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 12
Population: The ITT included all enrolled participants and received at least one dose of ozanimod. For paired segments analysis, any missing segment scores in the presence of at least 1 non-missing segmental SES-CD score were imputed by non-missing score used in the previous visit. If post-baseline SES-CD score was missing, then NRI was applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved an Endoscopic Response-50 (Paired Segment) Based on Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12 | 23.2 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 12
The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency (SF) and abdominal pain (AP) (rated on a scale of 0-3) assessed for 7 days. Clinical Remission (SF and AP remission) was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 12
Population: The ITT included all enrolled participants and received at least one dose of ozanimod. If stool frequency and abdominal pain were missing, then non-reesponder imputation (NRI) was applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 12 | 20.3 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 52
Clinical Remission is defined as the participants with the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days.
Time frame: Week 52
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. Observed cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 52 | 53.1 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Weeks 4 and 8
The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency (SF) and abdominal pain (AP) (rated on a scale of 0-3) assessed for 7 days. Clinical Remission (SF and AP remission) was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Weeks 4 and 8
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. If stool frequency and abdominal pain were missing, then non-reesponder imputation (NRI) was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Weeks 4 and 8 | Week 4 | 11.6 Percentage of Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Weeks 4 and 8 | Week 8 | 26.1 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 52
Clinical Remission is defined as a CDAI score of \< 150. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 52
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. Observed Cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 52 | 65.6 Percentage of Participants |
Other Pre-specified
Percentage of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 - Observed Cases
Endoscopic remission is defined as SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score \>1point. The SES-CD assesses 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 are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 52
Population: The ITT = all enrolled participants who received at least one dose of ozanimod. For Robarts Observed Score, the SES-CD score was determined based on all available segments at a given visit without adjusting for the segments available at baseline. Observed Cases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 - Observed Cases | 16.7 Percentage of Participants |
Other Pre-specified
Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 12
Clinical Remission is defined as a CDAI score of \< 150. The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Week 12
Population: The ITT included all enrolled participants and received at least one dose of ozanimod. If CDAI score was missing, then non-responder imputation (NRI) was applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 12 | 33.3 Percentage of Participants |
Other Pre-specified
Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Weeks 4 and 8
Clinical Remission is defined as a CDAI score of \< 150. The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.
Time frame: Weeks 4 and 8
Population: The ITT population included all enrolled participants who received at least one dose of ozanimod. Non-responder imputed. (NRI).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Weeks 4 and 8 | Week 4 | 15.9 Percentage of Participants |
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Weeks 4 and 8 | Week 8 | 23.2 Percentage of Participants |
Other Pre-specified
Percentage of Participants With RHI Healing at Week 52
Changes from baseline in intestinal mucosa histopathologic features and disease activity were assessed by blinded pathologists. Robarts Histopathology Index (RHI) had a maximum total score of 165, with higher scores indicating more severe histological disease. Baseline was defined as the last non-missing record on or before the first dose of study drug. The Robarts Histopathology Index (RHI) is a recently validated instrument that measures histological disease activity in ulcerative colitis. RHI Mucosal Healing was defined as a composite endpoint of being a responder for endoscopic remission and RHI remission.
Time frame: Week 52
Population: The ITT population = all enrolled participants who received at least one dose of ozanimod. Observed cases.. Analysis includes participants with data available at baseline and visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Percentage of Participants With RHI Healing at Week 52 | 14.3 Percentage of Participants |
Other Pre-specified
Pharmacokinetic Plasma Concentration of Ozanimod
Summary of concentrations of Ozanimod in RPC01-2201 by scheduled visit.
Time frame: From Day 1 to Week 52
Population: The intent to treat population = all enrolled participants who received at least one dose of ozanimod.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | Pharmacokinetic Plasma Concentration of Ozanimod | Day 1, post-dose | 48 pg/mL | Standard Deviation 19 |
| Ozanimod Hydrochloride (HCl) 1 mg | Pharmacokinetic Plasma Concentration of Ozanimod | Week 4 | 228 pg/mL | Standard Deviation 116 |
| Ozanimod Hydrochloride (HCl) 1 mg | Pharmacokinetic Plasma Concentration of Ozanimod | Week 8 | 195 pg/mL | Standard Deviation 102 |
| Ozanimod Hydrochloride (HCl) 1 mg | Pharmacokinetic Plasma Concentration of Ozanimod | Week 12 | 165 pg/mL | Standard Deviation 126 |
| Ozanimod Hydrochloride (HCl) 1 mg | Pharmacokinetic Plasma Concentration of Ozanimod | Week 24 | 190 pg/mL | Standard Deviation 109 |
| Ozanimod Hydrochloride (HCl) 1 mg | Pharmacokinetic Plasma Concentration of Ozanimod | Week 52 | 154 pg/mL | Standard Deviation 98 |
Other Pre-specified
PK Plasma Concentration of Active Metabolite CC-112273
Summary of concentrations of CC-112273 in RPC01-2201 by scheduled visit.
Time frame: From Day 1 to Week 52
Population: The intent to treat population = all enrolled participants who received at least one dose of ozanimod.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ozanimod Hydrochloride (HCl) 1 mg | PK Plasma Concentration of Active Metabolite CC-112273 | Day 1, post-dose | 58 pg/mL | Standard Deviation 41 |
| Ozanimod Hydrochloride (HCl) 1 mg | PK Plasma Concentration of Active Metabolite CC-112273 | Week 4 | 2348 pg/mL | Standard Deviation 1289 |
| Ozanimod Hydrochloride (HCl) 1 mg | PK Plasma Concentration of Active Metabolite CC-112273 | Week 8 | 3138 pg/mL | Standard Deviation 2129 |
| Ozanimod Hydrochloride (HCl) 1 mg | PK Plasma Concentration of Active Metabolite CC-112273 | Week 12 | 3507 pg/mL | Standard Deviation 2337 |
| Ozanimod Hydrochloride (HCl) 1 mg | PK Plasma Concentration of Active Metabolite CC-112273 | Week 24 | 4259 pg/mL | Standard Deviation 3322 |
| Ozanimod Hydrochloride (HCl) 1 mg | PK Plasma Concentration of Active Metabolite CC-112273 | Week 52 | 4055 pg/mL | Standard Deviation 3569 |