Clinical Trial Results:
A Phase 2, Multi-Center, Open-Label Induction Trial with Extension Period to Assess Endoscopic Improvement and Changes in Intestinal and Serum Biomarkers in Patients with Moderately to Severely Active Crohn's Disease Receiving Oral RPC1063 as Induction Therapy
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Summary
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EudraCT number |
2015-002025-19 |
Trial protocol |
HU PL IT |
Global end of trial date |
28 Nov 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Dec 2020
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First version publication date |
06 Dec 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RPC01-2201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02531113 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bristol-Myers Squibb
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Sponsor organisation address |
Chaussée de la Hulpe 185, Brussels, Belgium, 1170
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Public contact |
EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
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Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Nov 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Nov 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess endoscopic improvement following treatment with ozanimod
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Protection of trial subjects |
Patient Confidentiality, Informed Consent and Archival of Essential Documents
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Oct 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
37 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Poland: 10
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Country: Number of subjects enrolled |
Ukraine: 17
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Country: Number of subjects enrolled |
United States: 38
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Worldwide total number of subjects |
69
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EEA total number of subjects |
13
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
67
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Sixty-nine adult participants were enrolled from 28 sites located in Europe and North America. | ||||||||||||||||||
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Pre-assignment
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Screening 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. | ||||||||||||||||||
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Period 1
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Period 1 title |
Induction Period: Week 0 to 12
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Ozanimod Hydrochloride (HCl) 1 mg | ||||||||||||||||||
Arm description |
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). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
RPC1063
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Investigational medicinal product code |
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Other name |
Ozanimod
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
0.25 mg, 1 mg
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Period 2
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Period 2 title |
Extension Period: Week 12 up to Week 160
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Ozanimod Hydrochloride (HCl) 1 mg | ||||||||||||||||||
Arm description |
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). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
RPC1063
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Investigational medicinal product code |
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Other name |
Ozanimod
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
0.25 mg, 1 mg
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| Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 6 participants completed Induction Period, but did not proceed to Extension Period due to lack of efficacy |
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Baseline characteristics reporting groups
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Reporting group title |
Ozanimod Hydrochloride (HCl) 1 mg
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Reporting group description |
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). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ozanimod Hydrochloride (HCl) 1 mg
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Reporting group description |
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). | ||
Reporting group title |
Ozanimod Hydrochloride (HCl) 1 mg
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Reporting group description |
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). | ||
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End point title |
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. [1] | ||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Baseline to Week 12
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only summary statistics were planned for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
The Number of Participants with Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period | ||||||||||||||||||||||||||||||
End point description |
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
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End point type |
Secondary
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End point timeframe |
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
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Change in the Crohn's Disease Activity Index (CDAI) Score from Baseline at Week 12 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Baseline to Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 12 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who Achieved a Clinical Response Based on Crohn's Disease Activity Index (CDAI) at Week 12 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 12 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures from Baseline at Week 12 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
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) | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
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 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Roberts Intestinal Histopathology Index from Baseline (Paired Segments) at Week 12 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Improvement in Perianal and Enterocutaneous Fistulas | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 12
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| Notes [2] - Too few participants with perianal or enterocutaneous fistulas at baseline for meaningful evaluation |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 - Observed Cases | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who Achieved an Endoscopic Response-50 Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 | ||||||||
End point description |
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..
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End point type |
Other pre-specified
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End point timeframe |
Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who Achieved Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 52 | ||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants who Achieved a Clinical Response Based on CDAI at Week 52 | ||||||||
End point description |
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.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Week 52
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 52 | ||||||||
End point description |
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.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Week 52
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures from Baseline at Week 52 | ||||||||
End point description |
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.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Week 52
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants in Clinical Remission Based on CDAI and PRO2 Definitions who were off Corticosteroids at Week 52 of Those on Corticosteroids | ||||||||
End point description |
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.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Week 52
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Percentage of Participants with Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Weeks 4 and 8 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Weeks 4 and 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants who Achieved a Clinical Response Based on CDAI at Weeks 4 and 8 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Weeks 4 and 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Weeks 4 and 8 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Weeks 4 and 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures at Weeks 4 and 8 | ||||||||||||
End point description |
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.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Weeks 4 and Week 8
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percentage of Participants with RHI Healing at Week 52 | ||||||||
End point description |
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.
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.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Week 52
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Change in Fecal Calprotectin (Observed Cases) at Weeks 12 and 52 | ||||||||||||
End point description |
Change in fecal calprotectin (observed cases) determined by comparing measurements at weeks 12 and 52 to baseline measurement.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Baseline to Weeks 12 and Week 52
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change in Serum C-Reactive Protein (CRP) Levels from Baseline (Observed Cases) at Weeks 12 and 52 | ||||||||||||
End point description |
Change in Serum C-Reactive Protein was determined by comparing to baseline.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Baseline to Weeks 12 and 52
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Changes in Biomarkers: Percentage of Participants with CRP Response-10 - Non-responder Imputation | ||||||||||||
End point description |
The percentage of participants with a CRP Response-10 was assessed. CRP Response-10 is defined as C-reactive protein < 10 mg/L.
If any scores are missing then non-responder imputation is applied.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Week 12, Week 52
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Changes in Biomarkers: Percentage of Participants with FCP Response-250 - Non-responder Imputation | ||||||||||||
End point description |
The percentage of participants with a FCP Response-250 was assessed. FCP Response-250 is defined as Fecal calprotectin < 250 ug/g.
If any Fecal Calprotectin are missing then non-responder imputation is applied.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Week 12, Week 52
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Improvement in Perianal and Enterocutaneous Fistulas in Participants with Fistula's from Baseline at Weeks 4 and 8 | ||||||||
End point description |
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.
|
||||||||
End point type |
Other pre-specified
|
||||||||
End point timeframe |
Baseline to Week 4 and 8
|
||||||||
|
|||||||||
| Notes [3] - Too few participants with perianal or enterocutaneous fistulas at baseline for meaningful evaluation |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Pharmacokinetic Plasma Concentration of Ozanimod | ||||||||||||
End point description |
Pharmacokinetic structure and variability using the population modeling approach.
|
||||||||||||
End point type |
Other pre-specified
|
||||||||||||
End point timeframe |
Population PK based estimate for day 1 and steady state Caverage: Day 1 predose and prior to discharge (approximately 6 – 8 hour postdose), and at predose on week 4, 8 and 12 visits
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||
End point title |
Pharmacokinetic (PK) Plasma Concentration of Active Metabolite CC112273 | ||||||||||||||||
End point description |
PK structure and variability parameters estimated using the population modeling approach. Metabolite measured is CC112273.
|
||||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||||
End point timeframe |
Population PK based estimate for day 1 and steady state Caverage: Day 1 predose and prior to discharge (approximately 6 – 8 hour postdose), and at predose on week 4, 8 and 12 visits
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in Absolute Lymphocyte Count (ALC) Derived from Hematology Laboratory Results at Weeks 4, 8 and 12 | ||||||||||||||
End point description |
Change in Absolute Lymphocyte Count (ALC) from baseline was determined by comparied to baseline.
|
||||||||||||||
End point type |
Other pre-specified
|
||||||||||||||
End point timeframe |
Baseline up to Weeks 4, 8 and 12
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
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
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
|
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|
Reporting groups
|
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Reporting group title |
RPC1063 1.0 mg
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
15 Jul 2015 |
• Addition of clinically relevant cardiovascular condition to exclusion criterion (Exclusion Criterion 12) • Added section for Un-weighted Stool Frequency and Abdominal Pain • Added section for planned Data Safety Monitoring Board |
||
09 Jun 2017 |
• The extension period was extended by 48 weeks for a total trialstudy period of 160 weeks • The complete PE was to be performed at Week 160 rather than Week 112 • An additional PFT and OCT assessment was added at Week 112 |
||
29 May 2018 |
• A 75-day (±10 days) Safety Follow-up Visit was added. • Added the option for subjects who complete the Week 160 visit to enter the open label extension Phase 3 Crohn’s disease Study RPC01-3204. |
||
24 May 2019 |
• Change to safety follow up from 75 days to 90-day (±10 days) Safety Follow-up Visit |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
