Primary Outcome Measures: | |
1. |
Study 1: Percentage of Participants Achieving Clinical Remission Per Modified Mayo Score (MMS) at Week 12 [ Time Frame: Week 12 ]
The Modified Mayo Score (MMS) is a composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: Endoscopic subscore (ES), scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); Stool frequency subscore (SFS), scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and rectal bleeding subscore (RBS), scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS. |
2. |
Study 1: Percentage of Participants Achieving Clinical Remission Per MMS at Week 52 [ Time Frame: Week 52 ]
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS. |
3. |
Study 1: Percentage of Participants With One or More Adverse Events (AEs) [ Time Frame: Up to approximately 52 weeks ]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience an AE will be reported. |
4. |
Study 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE [ Time Frame: Up to approximately 52 weeks ]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported. |
5. |
Study 2: Percentage of Participants Achieving Clinical Remission Per MMS at Week 12 [ Time Frame: Week 12 ]
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS. |
6. |
Study 2: Percentage of Participants With One or More AEs [ Time Frame: Up to approximately 52 weeks ]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported. |
7. |
Study 2: Percentage of Participants Who Discontinued Study Intervention Due to an AE [ Time Frame: Up to approximately 52 weeks ]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported. |
Secondary Outcome Measures: | |
1. |
Study 1: Percentage of Participants Achieving Clinical Response Per Partial Modified Mayo Score (pMMS) at Week 2 [ Time Frame: Week 2 ]
The partial Modified Mayo Score (pMMS) is a composite score of UC disease activity on a scale of increasing severity from 0-6, calculated by summing two subscores: SFS, scored from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). Clinical response is defined as pMMS reduction of 1 or more points and 30% or more, plus a reduction of 1 or more points in RBS or an absolute RBS of 0 or 1. |
2. |
Study 1: Percentage of Participants With Endoscopic Improvement at Week 12 [ Time Frame: Week 12 ]
Endoscopic improvement is defined as Mayo endoscopic subscore (ES) of 0 or 1. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity. |
3. |
Study 1: Percentage of Participants Achieving a Clinical Response Per MMS at Week 12 [ Time Frame: Week 12 ]
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical response is defined as an MMS reduction of 2 or more points and 30% or more, plus a reduction of more than 1 point in RBS or an absolute RBS of 0 or 1. |
4. |
Study 1: Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement (HEMI) at Week 12 [ Time Frame: Week 12 ]
HEMI is defined as a Geboes score of 3.1 or less and ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). |
5. |
Study 1: Percentage of Participants Achieving Clinical Remission Per pMMS at Week 12 [ Time Frame: Week 12 ]
pMMS is a composite score of UC disease activity on a scale of increasing severity from 0-6, calculated by summing two subscores: SFS, scored from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). Clinical remission per pMMS is defined as an RBS of 0 and SFS of ≤1. |
6. |
Study 1: Percentage of Participants With Endoscopic Remission at Week 12 [ Time Frame: Week 12 ]
ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). Endoscopic remission is defined as an ES of 0. |
7. |
Study 1: Percentage of Participants Reporting No Bowel Urgency at Week 12 [ Time Frame: Week 12 ]
Bowel urgency is measured using an NRS, which rates bowel urgency on a 0-11 scale of increasing severity. Resolution is defined as a score of 0 or 1 in participants who had a baseline score of 3 or more. |
8. |
Study 1: Percentage of Participants Reporting No Abdominal Pain at Week 12 [ Time Frame: Week 12 ]
Abdominal pain is measured on a 0-4 NRS of increasing pain severity. Absence of abdominal pain is defined as a rating of 0. |
9. |
Study 1: Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week 12 [ Time Frame: Week 12 ]
The IBDQ measures health related quality of life in subjects with inflammatory bowel disease. It consists of 32 questions each with a graded response of 1 (worst) to 7 (best). The score ranges from 32 to 224. IBDQ remission is defined as a score of at least 170. |
10. |
Study 1: Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12 [ Time Frame: Baseline and Week 12 ]
The FACIT-Fatigue is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function, scored on a 0-52 point scale, with greater scores indicating a better fatigue-related quality of life. The change from baseline in FACIT-Fatigue score will be presented. |
11. |
Percentage of Diagnostic Assay Positive (Dx+) Participants Achieving Clinical Remission Per MMS at Week 12 [ Time Frame: Week 12 ]
Dx+ participants are those who meet protocol-specific diagnostic assay criteria during screening. The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS. |
12. |
Percentage of Dx+ Participants With Endoscopic Improvement at Week 12 [ Time Frame: Week 12 ]
Dx+ participants are those who meet protocol-specific diagnostic assay criteria during screening. Endoscopic improvement is defined as ES of 0 or 1. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity. |
13. |
Study 1: Percentage of Participants Achieving Histologic-Endoscopic Remission (HER) at Week 12 [ Time Frame: Week 12 ]
HER is defined as a Geboes score of less than 2 and ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). |
14. |
Study 1: Percentage of Participants with Endoscopic Improvement at Week 52 [ Time Frame: Week 52 ]
Endoscopic improvement is defined as ES of 0 or 1. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity. |
15. |
Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission Per MMS at Week 52 [ Time Frame: Week 52 ]
The Modified Mayo Score (MMS) is a composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: Endoscopic subscore (ES), scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); Stool frequency subscore (SFS), scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and rectal bleeding subscore (RBS), scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Corticosteroid-free clinical remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS, and no corticosteroid use for ≥90 days before Week 52. |
16. |
Study 1: Percentage of Participants Achieving HEMI at Week 52 [ Time Frame: Week 52 ]
HEMI is defined as a Geboes score of 3.1 or less and ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). |
17. |
Study 1: Percentage of Participants Achieving Clinical Remission Per pMMS at Week 52 [ Time Frame: Week 52 ]
pMMS is a composite score of UC disease activity on a scale of increasing severity from 0-6, calculated by summing two subscores: SFS, scored from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). Clinical remission per pMMS is defined as an RBS of 0 and SFS of ≤1. |
18. |
Study 1: Percentage of Participants Achieving Sustained Clinical Remission Per MMS at Both Week 12 and Week 52 [ Time Frame: Week 12 and Week 52 ]
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Sustained clinical remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS, at both Week 12 and Week 52. |
19. |
Study 1: Percentage of Participants Reporting No Bowel Urgency at Week 52 [ Time Frame: Week 52 ]
Bowel urgency is measured using an NRS, which rates bowel urgency on a 0-11 scale of increasing severity. Resolution is defined as a score of 0 or 1 in participants who had a baseline score of 3 or more. |
20. |
Study 1: Percentage of Participants Reporting No Abdominal Pain at Week 52 [ Time Frame: Week 52 ]
Abdominal pain is measured on a 0-4 NRS of increasing pain severity. Absence of abdominal pain is defined as a rating of 0. |
21. |
Study 1: Percentage of Participants With Endoscopic Remission at Week 52 [ Time Frame: Week 52 ]
ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). Endoscopic remission is defined as an ES of 0. |
22. |
Study 1: Percentage of Participants with Sustained Clinical Response Per MMS at Both Week 12 and Week 52 [ Time Frame: Week 12, and Week 52 ]
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Sustained clinical response is defined as an MMS reduction of 2 or more points and 30% or more, plus a reduction of more than 1 point in RBS or an absolute RBS of 0 or 1, at both Week 12 and Week 52. |
23. |
Study 1: Percentage of Participants with Sustained Endoscopic Improvement at Both Week 12 and Week 52 [ Time Frame: Week 12 and Week 52 ]
Sustained endoscopic improvement is defined as an ES of 0 or 1 at both Week 12 and Week 52. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity. |
24. |
Study 1: Percentage of Participants Achieving HER at Week 52 [ Time Frame: Week 52 ]
HER is defined as a Geboes score of less than 2 and ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). |
25. |
Study 1: Percentage of Participants Achieving IBDQ Remission at Week 52 [ Time Frame: Week 52 ]
The IBDQ measures health related quality of life in subjects with inflammatory bowel disease. It consists of 32 questions each with a graded response of 1 (worst) to 7 (best). The score ranges from 32 to 224. IBDQ remission is defined as a score of at least 170. |
26. |
Study 1: Change from Baseline in FACIT-Fatigue Score at Week 52 [ Time Frame: Baseline and Week 52 ]
The FACIT-Fatigue is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function, scored on a 0-52 point scale, with greater scores indicating a better fatigue-related quality of life. The change from baseline in FACIT-Fatigue score will be presented. |
27. |
Percentage of Dx+ Participants Achieving Clinical Remission Per MMS at Week 52 [ Time Frame: Week 52 ]
Dx+ participants are those who meet protocol-specific diagnostic assay criteria during screening. The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS. |
28. |
Percentage of Dx+ Participants With Endoscopic Improvement at Week 52 [ Time Frame: Week 52 ]
Dx+ participants are those who meet protocol-specific diagnostic assay criteria during screening. Endoscopic improvement is defined as ES of 0 or 1. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity. |
29. |
Study 2: Percentage of Participants with Clinical Response Per pMMS at Week 2 [ Time Frame: Week 2 ]
pMMS is a composite score of UC disease activity on a scale of increasing severity from 0-6, calculated by summing two subscores: SFS, scored from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). Clinical response is defined as pMMS reduction of 1 or more points and 30% or more, plus a reduction of 1 or more points in RBS or an absolute RBS of 0 or 1. |
30. |
Study 2: Percentage of Participants With Endoscopic Improvement at Week 12 [ Time Frame: Week 12 ]
Endoscopic improvement is defined as Mayo endoscopic subscore (ES) of 0 or 1. The ES measures UC severity based on endoscopy on a 0-3 scale of increasing severity. |
31. |
Study 2: Percentage of Participants Achieving a Clinical Response Per MMS at Week 12 [ Time Frame: Week 12 ]
The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical response is defined as an MMS reduction of 2 or more points and 30% or more, plus a reduction of more than 1 point in RBS or an absolute RBS of 0 or 1. |
32. |
Study 2: Percentage of Participants Achieving HEMI at Week 12 [ Time Frame: Week 12 ]
HEMI is defined as a Geboes score of 3.1 or less and ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). |
33. |
Study 2: Percentage of Participants Achieving Clinical Remission Per pMMS at Week 12 [ Time Frame: Week 12 ]
pMMS is a composite score of UC disease activity on a scale of increasing severity from 0-6, calculated by summing two subscores: SFS, scored from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); RBS, scored from 0 (no blood seen) to 3 (blood alone passed). Clinical remission per pMMS is defined as an RBS of 0 and SFS of ≤1. |
34. |
Study 2: Percentage of Participants With Endoscopic Remission at Week 12 [ Time Frame: Week 12 ]
ES measures UC severity based on endoscopy, scored from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration). Endoscopic remission is defined as an ES of 0. |
35. |
Study 2: Percentage of Participants Reporting No Bowel Urgency at Week 12 [ Time Frame: Week 12 ]
Bowel urgency is measured using a numeric rating scale (NRS), which rates bowel urgency on a 0-11 scale of increasing severity. |
36. |
Study 2: Percentage of Participants Reporting No Abdominal Pain at Week 12 [ Time Frame: Week 12 ]
Abdominal pain is measured on a 0-4 NRS of increasing pain severity. Absence of abdominal pain is defined as a rating of 0. |
37. |
Study 2: Percentage of Participants Achieving IBDQ Remission at Week 12 [ Time Frame: Week 12 ]
The IBDQ measures health related quality of life in subjects with inflammatory bowel disease. It consists of 32 questions each with a graded response of 1 (worst) to 7 (best). The score ranges from 32 to 224. IBDQ remission is defined as a score of at least 170. |
38. |
Study 2: Change from Baseline in FACIT-Fatigue Score at Week 12 [ Time Frame: Baseline and Week 12 ]
The FACIT-Fatigue is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function, scored on a 0-52 point scale, with greater scores indicating a better fatigue-related quality of life. The change from baseline in FACIT-Fatigue score will be presented. |
39. |
Study 2: Percentage of Participants Achieving HER at Week 12 [ Time Frame: Week 12 ]
HER is defined as a Geboes score of less than 2 and ES of 0 or 1. The Geboes score is a histologic grading system for inflammation in UC with scores ranging from 0 to 5.4, with higher scores indicating more severe inflammation. |