Ulcerative Colitis (UC)
Conditions
Keywords
Ulcerative Colitis
Brief summary
To evaluate safety and efficacy of two adalimumab dosing regimens for induction and maintenance (standard and higher dosing) in achieving clinical remission in subjects with moderately to severely active ulcerative colitis.
Interventions
DRUGAdalimumab
OTHERPlacebo
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Ulcerative Colitis (UC) for at least 90 days, confirmed by endoscopy during Screening period. * Active UC with Mayo Score of 6 to 12 points and endoscopy subscore of 2 to 3 despite concurrent or prior treatment with a full and adequate course, in the opinion of the Investigator, with oral corticosteroids or immunosuppressants or both. Mayo Score is confirmed by central reader.
Exclusion criteria
* Subject with Crohn's disease (CD) or indeterminate colitis (IC). * Current diagnosis of fulminant colitis and/or toxic megacolon. * Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy. * Chronic recurring infections or active tuberculosis (TB).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8 | Week 8 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1. |
| Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per FMS) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease from baseline in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8 | Week 8 | The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life. |
| Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8 | Week 8 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical response is defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. |
| Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8 | Week 8 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic remission is defined as an endoscopy subscore of 0. |
| Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8 | Week 8 | The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 6. |
| Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8 | Week 8 | The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1. |
| Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. |
| Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. |
| Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission is defined as FMS ≤ 2 with no subscore \> 1. |
| Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopy subscore provided by the central reader. |
| Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8 | Week 8 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. |
| Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. |
| Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. |
| Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life. |
| Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-responders are defined as participants not meeting the criteria of response (defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore \[RBS\] ≥ 1 or an absolute RBS ≤ 1) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. |
| Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-remitters are defined as participants not meeting the criteria of clinical remission at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. |
| Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per Full Mayo score) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic remission is defined as an endoscopy subscore of 0. |
| Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopic remission is defined as an endoscopy subscore of 0. |
| Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore \[RBS\] ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Bowel Symptom domain score range is 10 (severe problem) to 70 (normal health). Response is defined as increase of Bowel Symptom domain score ≥ 6 from baseline. |
| Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Response in IBDQ fatigue item (range 1 \[severe problem\] to 7 \[normal health\]) is defined as increase of IBDQ fatigue item ≥ 1 from baseline. |
| Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52 | Week 52 | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. Endoscopy subscore provided by the central reader. |
| Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8 | Week 8 | — |
Countries
Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Poland, Romania, Slovakia, Spain, Switzerland, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This study included a Main Study (120 sites in 19 countries) and a Japan Sub-Study (22 sites in Japan). After a 3-week screening period, participants were randomized 3:2 to an 8-week double-blind (DB) Induction Period with 2 adalimumab dosing regimens (Induction Standard Dose \[I-SD\] or Induction Higher Dose \[I-HD\]).
Pre-assignment details
At Week 8, participants in Main Study were re-randomized (2:2:1) into 44-week DB Maintenance Period with 3 adalimumab dosing regimens (M-SD, M-HD, or an exploratory Therapeutic Drug Monitoring \[TDM\] Regimen). Participants in Japan Sub-study were re-randomized (1:1) into 44-week DB Maintenance Period with 2 adalimumab dosing regimens (M-SD, M-HD).
Participants by arm
| Arm | Count |
|---|---|
| Induction (Main Study + Japan Sub-study): I-SD Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6. | 379 |
| Induction (Main Study + Japan Sub-study): I-HD Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6. | 573 |
| Total | 952 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Induction Study | Adverse Event | 13 | 19 | 0 | 0 | 0 |
| Induction Study | Lack of Efficacy | 22 | 27 | 0 | 0 | 0 |
| Induction Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Induction Study | Other, Not Specified | 3 | 2 | 0 | 0 | 0 |
| Induction Study | Requires Alternative/Prohibited Therapy | 4 | 5 | 0 | 0 | 0 |
| Induction Study | Subject Noncompliance | 1 | 1 | 0 | 0 | 0 |
| Induction Study | Withdrawal by Subject | 3 | 5 | 0 | 0 | 0 |
| Maintenance Study | Adverse Event | 0 | 0 | 25 | 22 | 11 |
| Maintenance Study | Lack of Efficacy | 0 | 0 | 70 | 55 | 19 |
| Maintenance Study | Lost to Follow-up | 0 | 0 | 4 | 1 | 1 |
| Maintenance Study | Other, Not Specified | 0 | 0 | 6 | 14 | 2 |
| Maintenance Study | Requires Alternative/Prohibited Therapy | 0 | 0 | 7 | 3 | 4 |
| Maintenance Study | Subject Non-Compliance | 0 | 0 | 1 | 3 | 2 |
| Maintenance Study | Unknown Reason | 0 | 0 | 0 | 1 | 0 |
| Maintenance Study | Withdrawal by Subject | 0 | 0 | 11 | 5 | 7 |
Baseline characteristics
| Characteristic | Induction (Main Study + Japan Sub-study): I-SD | Induction (Main Study + Japan Sub-study): I-HD | Total |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 13.14 | 40.5 years STANDARD_DEVIATION 12.89 | 40.4 years STANDARD_DEVIATION 12.98 |
| FMS: Rectal Bleeding Subscore | 1.68 units on a scale STANDARD_DEVIATION 0.955 | 1.75 units on a scale STANDARD_DEVIATION 0.967 | 1.72 units on a scale STANDARD_DEVIATION 0.962 |
| Full Mayo Score (FMS) | 8.69 units on a scale STANDARD_DEVIATION 1.509 | 8.87 units on a scale STANDARD_DEVIATION 1.571 | 8.80 units on a scale STANDARD_DEVIATION 1.548 |
| Race/Ethnicity, Customized Asian | 44 Participants | 70 Participants | 114 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 16 Participants | 24 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 19 Participants | 28 Participants | 47 Participants |
| Race/Ethnicity, Customized Japanese | 39 Participants | 61 Participants | 100 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 321 Participants | 484 Participants | 805 Participants |
| Race/Ethnicity, Customized White | 326 Participants | 484 Participants | 810 Participants |
| Region Non-United States | 314 Participants | 460 Participants | 774 Participants |
| Region United States | 65 Participants | 113 Participants | 178 Participants |
| Sex: Female, Male Female | 166 Participants | 239 Participants | 405 Participants |
| Sex: Female, Male Male | 213 Participants | 334 Participants | 547 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 379 | 4 / 573 | 2 / 345 | 2 / 350 | 0 / 151 |
| other Total, other adverse events | 74 / 379 | 112 / 573 | 140 / 345 | 141 / 350 | 47 / 151 |
| serious Total, serious adverse events | 19 / 379 | 22 / 573 | 44 / 345 | 44 / 350 | 15 / 151 |
Outcome results
Primary
Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1.
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8 | 10.9 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8 | 13.3 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8 | 11.6 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8 | 13.8 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.26995% CI: [-2, 7]Cochran-Mantel-Haenszel
p-value: 0.447Breslow-Day test
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.30195% CI: [-2, 6.6]Cochran-Mantel-Haenszel
p-value: 0.502Breslow-Day test
Primary
Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per FMS) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease from baseline in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore \> 1.
Time frame: Week 52
Population: ITT-Responder population (I-ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 29.0 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 39.5 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 30.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 41.1 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.06995% CI: [-0.8, 20.6]Cochran-Mantel-Haenszel
p-value: 0.085Breslow-Day test
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.04595% CI: [0.2, 20.4]Cochran-Mantel-Haenszel
p-value: 0.106Breslow-Day test
Secondary
Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8 | 27.1 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8 | 31.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8 | 26.9 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8 | 30.5 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.18195% CI: [-2, 10.5]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.295% CI: [-2, 9.7]Cochran-Mantel-Haenszel
Secondary
Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8 | 27.1 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8 | 31.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8 | 26.9 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8 | 30.5 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.395% CI: [-2.6, 8.6]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.25495% CI: [-2.2, 8.4]Cochran-Mantel-Haenszel
Secondary
Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8
The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8 | 60.9 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8 | 67.2 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8 | 60.7 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8 | 65.3 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.0595% CI: [0, 13.1]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.13195% CI: [-1.4, 11]Cochran-Mantel-Haenszel
Secondary
Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical response is defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1.
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8 | 40.0 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8 | 47.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8 | 38.8 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8 | 47.3 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.03595% CI: [0.5, 14.1]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.00895% CI: [2.3, 15.1]Cochran-Mantel-Haenszel
Secondary
Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic remission is defined as an endoscopy subscore of 0.
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8 | 10.0 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8 | 13.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8 | 10.0 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8 | 12.9 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.1695% CI: [-1.3, 7.6]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.16695% CI: [-1.2, 7.1]Cochran-Mantel-Haenszel
Secondary
Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8
The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 6.
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8 | 63.2 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8 | 71.3 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8 | 63.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8 | 69.8 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.01195% CI: [1.9, 14.7]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.02595% CI: [0.9, 13]Cochran-Mantel-Haenszel
Secondary
Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8
The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1.
Time frame: Week 8
Population: Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8 | 57.1 percentage of participants |
| Induction (Main Study): I-HD | Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8 | 61.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8 | 57.5 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8 | 59.9 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.21895% CI: [-2.5, 10.9]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.p-value: 0.45695% CI: [-4, 8.8]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-remitters are defined as participants not meeting the criteria of clinical remission at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.
Time frame: Week 52
Population: ITT-Non-Remitter (ITT-NRM) Population: all participants in ITT who did not achieve Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52 | 17.4 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52 | 22.9 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52 | 17.0 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52 | 23.8 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.12195% CI: [-1.4, 12.1]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.04695% CI: [0.1, 12.8]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per Full Mayo score) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic remission is defined as an endoscopy subscore of 0.
Time frame: Week 52
Population: ITT-RP: participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants who were remitters at Week 8. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 27.6 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 35.5 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 27.0 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 35.4 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.15995% CI: [-2.9, 17.9]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.10995% CI: [-1.8, 17.9]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopic remission is defined as an endoscopy subscore of 0.
Time frame: Week 52
Population: ITT-Remitter (ITT-RM) Population: all participants in ITT who achieved Week 8 remission based on the Full Mayo Score utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 45.9 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 47.6 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 42.2 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52 | 44.2 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.90395% CI: [-21, 23.8]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.90195% CI: [-18.8, 21.3]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore \[RBS\] ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Bowel Symptom domain score range is 10 (severe problem) to 70 (normal health). Response is defined as increase of Bowel Symptom domain score ≥ 6 from baseline.
Time frame: Week 52
Population: ITT-Responder population (ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52 | 62.1 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52 | 69.7 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52 | 62.6 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52 | 71.4 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.1695% CI: [-3, 18.4]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.07695% CI: [-0.9, 19.1]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Response in IBDQ fatigue item (range 1 \[severe problem\] to 7 \[normal health\]) is defined as increase of IBDQ fatigue item ≥ 1 from baseline.
Time frame: Week 52
Population: ITT-Responder population (ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52 | 53.8 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52 | 61.2 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52 | 55.2 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52 | 59.4 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.20795% CI: [-4, 18.6]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.4495% CI: [-6.4, 14.8]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.
Time frame: Week 52
Population: ITT-Responder population (I-ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52 | 41.4 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52 | 51.3 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52 | 41.7 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52 | 52.0 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.09895% CI: [-1.7, 20.8]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.06695% CI: [-0.7, 20.5]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1.
Time frame: Week 52
Population: I-ITT-RP: participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid use at Baseline. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 53.3 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 74.7 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 54.4 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 74.1 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.00295% CI: [7.6, 35.4]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.00395% CI: [6.6, 32.7]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission is defined as FMS ≤ 2 with no subscore \> 1.
Time frame: Week 52
Population: I-ITT-RP: participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid use at Baseline. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52 | 27.2 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52 | 38.9 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52 | 28.2 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52 | 39.8 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.09395% CI: [-1.9, 25]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.08895% CI: [-1.7, 23.8]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopy subscore provided by the central reader.
Time frame: Week 52
Population: ITT-Remitter (ITT-RM) Population included all participants in the ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 40.5 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 57.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 44.4 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52 | 55.8 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.16195% CI: [-6.3, 38.2]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.31295% CI: [-9.8, 30.6]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. Endoscopy subscore provided by the central reader.
Time frame: Week 52
Population: ITT-Remitter (ITT-RM) Population included all participants in the ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52 | 51.4 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52 | 64.3 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52 | 55.6 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52 | 61.5 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.27295% CI: [-9.7, 34.4]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.695% CI: [-14.6, 25.2]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.
Time frame: Week 52
Population: ITT-RM Population: participants in ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid use at Baseline. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 53.8 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 77.8 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 56.3 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52 | 71.4 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.07495% CI: [-2.3, 49.9]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.2195% CI: [-8.5, 38.4]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.
Time frame: Week 52
Population: ITT-RM Population: all participants in the ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid usage. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52 | 34.6 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52 | 55.6 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52 | 37.5 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52 | 51.4 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.15195% CI: [-7.3, 47.3]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.29995% CI: [-11.3, 36.8]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.
Time frame: Week 52
Population: ITT-Responder population (ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52 | 62.1 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52 | 66.4 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52 | 62.6 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52 | 65.7 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.42295% CI: [-6.4, 15.3]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.51395% CI: [-6.8, 13.6]Cochran-Mantel-Haenszel
Secondary
Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52
The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy \[confirmed by a central reader\], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-responders are defined as participants not meeting the criteria of response (defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore \[RBS\] ≥ 1 or an absolute RBS ≤ 1) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore \> 1.
Time frame: Week 52
Population: ITT-Non-Responder (ITT-NRP) Population: all participants in ITT who did not achieve Week 8 response based on the Full Mayo Score utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction (Main Study): I-SD | Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52 | 12.1 percentage of participants |
| Induction (Main Study): I-HD | Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52 | 15.8 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-SD | Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52 | 12.1 percentage of participants |
| Induction (Main Study + Japan Sub-study): I-HD | Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52 | 16.0 percentage of participants |
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.35195% CI: [-4.1, 11.4]Cochran-Mantel-Haenszel
Comparison: Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.p-value: 0.29295% CI: [-3.3, 11.1]Cochran-Mantel-Haenszel