Primary Outcomes

Description: Treatment-emergent adverse events are defined as events that begin or worsen either on or after the first dose of the study drug and within 30 days after the last dose of the study drug in the analysis period.

Measure: Assessing Treatment-Emergent Adverse Events

Time: Up to 288 Weeks

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Primary Outcomes

Description: Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 2 years of randomized treatment

Measure: Proportion of patients in sustained clinical remission

Time: 2 years

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Secondary Outcomes

Description: Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 4 years of randomized treatment

Measure: Proportion of patients in sustained clinical remission

Time: 4 years

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Description: Relapse time

Measure: Time from randomization to relapse

Time: 2 years

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Description: Relapse time

Measure: Time from randomization to relapse

Time: 4 years

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Description: Remission, but no need to restart anti-tnf therapy

Measure: Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy

Time: 2 years

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Description: Remission, but no need to restart anti-tnf therapy

Measure: Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy

Time: 4 years

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Description: Remission after relapse

Measure: Proportion of relapse patients achieving remission after anti-TNF restart

Time: 2 years

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Description: Remission after relapse

Measure: Proportion of relapse patients achieving remission after anti-TNF restart

Time: 4 years

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Description: Adverse events

Measure: Adverse events and serious adverse events frequency and severity

Time: 2 years

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Description: Adverse events

Measure: Adverse events and serious adverse events frequency and severity

Time: 4 years

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Primary Outcomes

Description: Remission is defined as a composite score of patient-reported symptoms using daily ediary and centrally read endoscopy as stool frequency subscore of 0 or 1 with at least a 1-point change from baseline, rectal bleeding subscore of 0 and endoscopic subscore of 0 or 1 (modified, excludes friability). The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA: 0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

Measure: Number of Participants With Remission at Week 12

Time: Week 12

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Secondary Outcomes

Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

Measure: Number of Participants With Endoscopic Remission at Week 12

Time: Week 12

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Description: Clinical remission is defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0. The stool frequency subscore and rectal bleeding subscore range from 0 to 3 with higher scores indicating more severe disease.

Measure: Number of Participants With Clinical Remission at Week 4, 8, 12

Time: Week 4, 8, 12

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Description: Clinical response (composite) is defined as a decrease from baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the subscore for rectal bleeding greater than or equal to (>=) 1 point or a subscore for rectal bleeding less than or equal to (<=) 1. The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

Measure: Number of Participants With Clinical Response (Composite) at Week 12

Time: Week 12

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Description: Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of <=2. The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

Measure: Number of Participants With Mucosal Healing at Week 12

Time: Week 12

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Description: Remission is defined as a total mayo score of less than or equal to <=2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and PGA) exceeding 1, at the Week 12. The total mayo score ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

Measure: Number of Participants With Remission Based on Total Mayo Score at Week 12

Time: Week 12

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Description: Clinical response (Mayo) is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding >=1 point or an absolute subscore for rectal bleeding <=1. The total mayo score ranges from 0 to 12 points and consists of the following 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

Measure: Number of Participants With Clinical Response Based on Total Mayo Score at Week 12

Time: Week 12

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Description: The partial mayo score ranges from 0 to 9 points and consists of the following 3 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); PGA (0-3). The partial Mayo score does not include the endoscopy subscore. Here participants with partial Mayo score <= 2 with no individual subscore >1 at the Week 4, 8, and 12 will be assessed.

Measure: Number of Participants With Partial Mayo Score Less than or Equal to (<=) 2 with no Individual Subscore Greater than (>) 1 at Week 4, 8, 12

Time: Week 4, 8, 12

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Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Here number of participants with endoscopic remission at week 12 with a subscore of 0 will be assessed.

Measure: Number of Participants with Endoscopic Remission at Week 12 With Endoscopic Subscore of 0

Time: Week 12

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Description: Clinical remission with both rectal bleeding and stool frequency subscores of 0 at week 4, 8, 12 will be assessed. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

Measure: Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Subscores of 0 at Week 4, 8, 12

Time: Week 4, 8, 12

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Description: Deep remission is defined as both endoscopic and rectal bleeding subscores of 0, and stool frequency subscore <=1 and a centrally read Geboes score of <=2.. The stool frequency subscore, rectal bleeding subscore and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

Measure: Number of Participants With Deep Remission at Week 12

Time: Week 12

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Description: Participants will be asked to record the abdominal pain worst severity using 0-10 numeric rating scale, with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Abdominal Pain Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the diarrhea frequency (enter number of loose or watery bowel movements) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Diarrhea Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the urgency frequency (enter number of bowel movements with urgency) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Urgency Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the stool frequency (enter number of bowel movements passed) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Absolute Stool Frequency Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the rectal bleeding severity and frequency (enter number of bowel movements with blood) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Absolute Rectal Bleeding Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: The total sign/symptom score (average of rectal bleeding, stool frequency, abdominal pain, diarrhea, and urgency) ranges from 0 to 10 with higher scores indicating higher severity.

Measure: Change From Baseline Total Sign/Symptom Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: The IBDQ is a psychometrically validated participant-reported outcome (PRO) instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, including UC. The IBDQ consists of 32 items, which are grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains are scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement.

Measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains and Total Absolute Scores in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 8, 12

Time: Baseline, Week 8, 12

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Description: The SF-36 is a generic quality-of-life instrument that has been widely used to assess health-related quality of life (HRQL) of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

Measure: Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores and Individual Domain Scores) at Week 12

Time: Baseline, Week 12

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Description: Incidence of hospitalizations during the entire study period will be assessed.

Measure: Incidence of Hospitalizations

Time: From start of study up to follow up (Week 29)

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Description: Incidence of total inpatient days during the entire study period will be assessed.

Measure: Incidence of Total Inpatient Days

Time: From start of study up to follow up (Week 29)

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Primary Outcomes

Description: Remission is defined as a composite score of participant-reported symptoms using daily e-diary and centrally read endoscopy as stool frequency subscore of 0 or 1 with at least a 1-point change from baseline, rectal bleeding subscore of 0 and endoscopic subscore of 0 or 1 (modified, excludes friability). The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); Physician global assessment (PGA: 0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

Measure: Number of Participants With Remission at Week 12

Time: Week 12

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Secondary Outcomes

Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease.

Measure: Number of Participants With Endoscopic Remission at Week 12

Time: Week 12

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Description: Clinical remission is defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0. The stool frequency subscore and rectal bleeding subscore range from 0 to 3 with higher scores indicating more severe disease.

Measure: Number of Participants With Clinical Remission at Week 4, 8, 12

Time: Week 4, 8, 12

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Description: Clinical response (composite) is defined as a decrease from baseline in the composite score of participant-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30 percent (%), with an accompanying decrease in the subscore for rectal bleeding greater than or equal to (>=) 1 point or a subscore for rectal bleeding less than or equal to (<=) 1. The Mayo score is a measure of UC disease activity. It ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease The subscores are Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3). The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

Measure: Number of Participants With Clinical Response (Composite) at Week 12

Time: Week 12

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Description: Mucosal healing is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of <=2. The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

Measure: Number of Participants With Mucosal Healing at Week 12

Time: Week 12

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Description: Remission is defined as a total mayo score of less than or equal to <=2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and physician's global assessment) exceeding 1, at the Week 12. The total mayo score ranges from 0 to 12 points and consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

Measure: Number of Participants With Remission Based on Total Mayo Score at Week 12

Time: Week 12

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Description: Clinical response (Mayo) is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding >=1 point or an absolute subscore for rectal bleeding <=1. The total mayo score ranges from 0 to 12 points and consists of the following 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); Findings of endoscopy (0-3); PGA (0-3).

Measure: Number of Participants With Clinical Response Based on Total Mayo Score at Week 12

Time: Week 12

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Description: The partial mayo score ranges from 0 to 9 points and consists of the following 3 subscores, each graded from 0 to 3 with higher scores indicating more severe disease: Stool frequency (0-3); Rectal bleeding (0-3); PGA (0-3). The partial Mayo score does not include the endoscopy subscore. Number of participants with partial mayo score <=2 with no individual subscore >1 at the Week 4, 8, 12 will be assessed.

Measure: Number of Participants With Partial Mayo Score Less than or Equal (<=) 2 with no individual subscore Greater than (>) 1 at Week 4, 8, 12

Time: Week 4, 8, 12

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Description: Endoscopic remission is defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability). The centrally read endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. Here number of participants with endoscopic remission at week 12 with a subscore of 0 will be assessed.

Measure: Number of Participants with Endoscopic Remission at Week 12 With Endoscopic Subscore of 0

Time: Week 12

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Description: Clinical remission with both rectal bleeding and stool frequency subscores of 0 at week 4, 8, 12 will be assessed. The stool frequency subscore and rectal bleeding subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points.

Measure: Number of Participants With Clinical Remission With Both Rectal Bleeding and Stool Frequency Subscores of 0 at Week 4, 8, 12

Time: Week 4, 8, 12

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Description: Deep remission is defined as both endoscopic and rectal bleeding subscores of 0, and stool frequency subscore <=1 and a centrally read Geboes score of <=2.. The stool frequency subscore, rectal bleeding subscore and endoscopic subscore of mayo score ranges from 0 to 3 with higher scores indicating more severe disease. The composite score is a recommended measure consisting of the Mayo score without the PGA subscore and ranges from 0 to 9 points. Geboes score grading system, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher geboes score indicates more severe disease.

Measure: Number of Participants With Deep Remission at Week 12

Time: Week 12

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Description: Participants will be asked to record the abdominal pain worst severity using 0-10 numeric rating scale, with 0 anchor at "No pain" and 10 at "Worst Imaginable Pain" as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Abdominal Pain Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the diarrhea frequency (enter number of loose or watery bowel movements) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Diarrhea Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the urgency frequency (enter number of bowel movements with urgency) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Urgency Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the stool frequency (enter number of bowel movements passed) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Absolute Stool Frequency Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: Participants will be asked to record the rectal bleeding severity and frequency (enter number of bowel movements with blood) as experienced over the previous 24 hours, in the e-diary.

Measure: Change From Baseline in Absolute Rectal Bleeding Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: The total sign/symptom score (average of rectal bleeding, stool frequency, abdominal pain, diarrhea, and urgency) ranges from 0 to 10 with higher scores indicating higher severity.

Measure: Change From Baseline Total Sign/Symptom Score Based on Participant e-Diary at Week 12

Time: Baseline, Week 12

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Description: The IBDQ is a psychometrically validated participant-reported outcome (PRO) instrument for measuring the disease-specific HRQL in participants with inflammatory bowel disease, including UC. The IBDQ consists of 32 items, which are grouped into 4 dimensions: bowel function, emotional status, systemic symptoms, and social function. The 4 domains are scored as follows: Bowel symptoms: 10 to 70; Systemic symptoms: 5 to 35; Emotional function: 12 to 84; Social function: 5 to 35. The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement.

Measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Domains and Total Absolute Scores in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 8, 12

Time: Baseline, Week 8, 12

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Description: The SF-36 is a generic quality-of-life instrument that has been widely used to assess health-related quality of life (HRQL) of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL.

Measure: Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores and Individual Domain Scores) at Week 12

Time: Baseline, Week 12

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Description: Incidence of hospitalizations during the entire study period will be assessed.

Measure: Incidence of Hospitalizations

Time: From start of study up to follow up (Week 29)

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Description: Incidence of total inpatient days during the entire study period will be assessed.

Measure: Incidence of Total Inpatient Days

Time: From start of study up to follow up (Week 29)

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Primary Outcomes

Description: Clinical remission per Adapted Mayo Score.

Measure: Sub-Study 1: Percentage of Participants with Clinical Remission per Adapted Mayo Score

Time: Week 52

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Secondary Outcomes

Description: Endoscopic remission per endoscopy subscore.

Measure: Sub-Study 1: Percentage of Participants with Endoscopic Remission

Time: Week 52

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Description: Clinical remission per full Mayo Score.

Measure: Sub-Study 1: Percentage of Participants with Clinical Remission per Full Mayo Score in Participants with a Full Mayo Score of 6 to 12 at Baseline (of Induction)

Time: Week 52

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Description: Clinical remission per Adapted Mayo Score.

Measure: Sub-Study 1: Percentage of Participants who Discontinued Corticosteroid Use, Remained Corticosteroid Free for 90 days, and Achieved Clinical Remission per Adapted Mayo Score in Participants Taking Steroids at Baseline (of induction).

Time: Week 52

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Description: Clinical remission per Adapted Mayo Score.

Measure: Sub-Study 1: Percentage of Participants with Clinical Remission per Adapted Mayo Score in Participants with a Clinical Remission at Week 0

Time: Week 52

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Description: Participants who discontinued corticosteroid use.

Measure: Sub-Study 1: Percentage of Participants who Discontinued Corticosteroid Use in Participants who were Taking Steroids at Baseline (of induction)

Time: Week 52

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Description: Endoscopic improvement per endoscopy subscore.

Measure: Sub-Study 1: Percentage of Participants with Endoscopic Improvement in Participants with Endoscopic Improvement at Week 0

Time: Week 52

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Description: Clinical response per Adapted Mayo score.

Measure: Sub-Study 1: Percentage of Participants with Clinical Response per Adapted Mayo Score

Time: Week 52

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Description: Endoscopic improvement per endoscopy subscore.

Measure: Sub-Study 1: Percentage of Participants with Endoscopic Improvement

Time: Week 52

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Description: Participants with an event that results in admission to the hospital.

Measure: Sub-Study 1: Percentage of Participants with Hospitalization

Time: Through Week 52

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Description: The UC-SQ is a patient questionnaire to assess severity of ulcerative colitis symptoms.

Measure: Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ)

Time: Week 0 to Week 52

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Description: Histologic remission per Geboes Score.

Measure: Sub-Study 1: Percentage of Participants with Histologic Remission

Time: Week 52

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Description: Mucosal healing defined as endoscopic and histologic remission.

Measure: Sub-Study 1: Percentage of Participants with Mucosal Healing

Time: Week 52

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Description: The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.

Measure: Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ)

Time: Week 0 to Week 52

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Description: Participants who underwent surgery related to UC.

Measure: Sub-Study 1: Percentage of Participants with Ulcerative Colitis (UC)-Related Surgeries

Time: Through Week 52

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Description: The SF-36 is an indicator of overall health status.

Measure: Sub-Study 1: Change in 36-Item Short Form Health Status Survey (SF-36)

Time: Week 0 to Week 52

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Description: The FACIT-Fatigue is a validated tool that measures an individual's level of fatigue during their usual daily activities over the past week.

Measure: Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Time: Week 0 to Week 52

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Description: The SFS, RBS, and endoscopic subscore describe disease severity.

Measure: Sub-Study 1: Percentage of Participants with Stool Frequency Subscore (SFS), Rectal Bleeding Subscore (RBS), and Endoscopic Subscore of 0

Time: At Week 52

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Description: The Stool Frequency Subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Stool Frequency Subscore indicates improvement.

Measure: Sub-Study 1: Percentage of Participants with Stool Frequency Subscore (SFS) ≤ 1

Time: Through Week 52

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Description: The Rectal Bleeding Subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Rectal Bleeding Subscore indicates improvement.

Measure: Sub-Study 1: Percentage of Participants with Rectal Bleeding Subscore (RBS) = 0

Time: Through Week 52

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Description: The Partial Adapted Mayo Score is a composite of the following sub-scores: SFS and RBS.

Measure: Sub-study 1: Change from Baseline of Induction in Partial Adapted Mayo Score

Time: Through Week 52

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Description: The Full Mayo Score ranges determines disease severity. A negative change in Full Mayo Score indicates improvement.

Measure: Sub-Study 1: Change in Full Mayo Score

Time: Week 0 to Week 52

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Description: The Stool Frequency Subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Stool Frequency Subscore indicates improvement.

Measure: Sub-Study 1: Change in SFS

Time: Week 0 to Week 52

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Description: The Rectal Bleeding Subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Rectal Bleeding Subscore indicates improvement.

Measure: Sub-Study 1: Change in RBS

Time: Week 0 to Week 52

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Description: High sensitivity C-reactive protein was analyzed by a central laboratory. The median percent change from week 0 in CRP is assessed at each time point.

Measure: Sub-Study 1: Change in High Sensitivity C-reactive Protein (hs-CRP)

Time: Week 0 to Week 52

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Description: Stool samples were analyzed by a central laboratory for fecal calprotectin (FCP)qualitative measurement. Results are reported for participants in each category.

Measure: Sub-Study 1: Change in Fecal Calprotectin (FCP)

Time: Week 0 to Week 52

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Description: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is defined as an assessment of the endoscopy findings scoring system for additional exploratory analyses.

Measure: Sub-Study 1: Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS)

Time: At Week 52

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Description: The European Quality of Life 5 Dimensions (EQ-5D-5L) is a standardized instrument used to measure health-related quality of life that can be used in a wide range of health conditions and treatments.

Measure: Sub-Study 1: Change in European Quality of Life 5 Dimensions (EQ-5D-5L)

Time: Week 0 to Week 52

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Description: The WPAI UC questionnaire was used to assess work and activity impairment due to symptoms of ulcerative colitis. The self-administered questionnaire measures the effect of the participant's health problems on work and daily activities in the previous week, specifically, the number of hours missed from work due to health problems, how much the subject's health problems affected work productivity, and how much the subject's health problems affected regular activities. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement.

Measure: Sub-Study 1: Change in Work Productivity and Impairment Questionnaire - UC (WPAI UC)

Time: Week 0 to Week 52

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Description: The Partial Adapted Mayo Score is a composite of the following sub-scores: SFS and RBS.

Measure: Sub-study 1: Time to Loss of Clinical Response per Partial Adapted Mayo in Patients with Response per Partial Adapted Mayo

Time: At Week 0

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Description: The PGIS is a response scale that describes the severity of the participants disease.

Measure: Sub-Study 1: Change in Patient Global Impression of Severity (PGIS)

Time: Week 0 to Week 52

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Description: The PGIC is a response scale. The participant will be asked by the Investigator or qualified designee to rate their change in their disease status.

Measure: Sub-Study 1: Change in Patient Global Impression of Change (PGIC) scores

Time: Through Week 52

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Description: Participants who discontinued corticosteroid use, in participants taking steroids at baseline (of induction).

Measure: Sub-Study 1: Percentage of Participants who Discontinued Corticosteroid Use, in Participants Taking Steroids at Baseline (of Induction).

Time: Through Week 52

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Description: Clinical remission per Adapted Mayo score, in participants taking steroids at baseline (of induction).

Measure: Sub-Study 1: Percentage of Participants who Discontinued Corticosteroid Use and Achieved Clinical Remission, in Participants Taking Steroids at Baseline (of Induction).

Time: Through Week 52

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Description: Clinical remission per Adapted Mayo score, in participants taking steroids at baseline (of induction).

Measure: Sub-Study 1: Percentage of Participants who Discontinued Corticosteroid Use for 90 Days and Achieved Clinical Remission, in Participants Taking Steroids at Baseline (of Induction).

Time: Through Week 52

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Description: Clinical remission per Adapted Mayo score, in participants taking steroids at baseline (of induction).

Measure: Sub-Study 1: Percentage of Participants who Discontinued Corticosteroid Use for 90 Days and SFS ≤ 1 (and not Worse than Baseline of Induction) and RBS = 1 and Achieved Clinical Remission, in Participants Taking Steroids at Baseline (of Induction).

Time: Through Week 52

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Description: The Partial Adapted Mayo Score is a composite of the following sub-scores: SFS and RBS.

Measure: Sub-Study 3: Percentage of Participants with Clinical Response per Partial Adapted Mayo Score

Time: Through Week 300

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Description: Clinical remission per Adapted Mayo Score.

Measure: Sub-Study 3: Percentage of Participants with Clinical Remission per Adapted Mayo Score with Endoscopy

Time: Through Week 300

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Description: Clinical response per Adapted Mayo score.

Measure: Sub-Study 3: Percentage of Participants with Clinical Response per Adapted Mayo Score with Endoscopy

Time: Through Week 300

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Description: The Partial Adapted Mayo Score is a composite of the following sub-scores: SFS and RBS.

Measure: Sub-Study 3: Time to Loss of Clinical Response per Partial Mayo Score

Time: Through Week 300

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Description: Clinical remission per Adapted Mayo Score.

Measure: Sub-Study 3: Time to Loss of Clinical Remission per Adapted Mayo Score with Endoscopy

Time: Through Week 300

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Description: Clinical response per Adapted Mayo score.

Measure: Sub-Study 3: Time too Loss of Clinical Response per Adapted Mayo Score with Endoscopy

Time: Through Week 300

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Description: The Partial Adapted Mayo Score is a composite of the following sub-scores: SFS and RBS, in participants taking steroids at baseline (of induction).

Measure: Sub-Study 3: Percentage of Participants Who Discontinued Corticosteroid Use with Clinical Response per Partial Adapted Mayo Score in Participants Taking Steroids at Baseline (of Induction).

Time: Through Week 300

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Description: Endoscopic improvement per endoscopy subscore.

Measure: Sub-Study 3: Percentage of Participants with Endoscopic Improvement

Time: Through Week 300

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Description: Endoscopic remission per endoscopy subscore.

Measure: Sub-Study 3: Percentage of Participants with Endoscopic Remission

Time: Through Week 300

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Description: Mucosal healing defined as endoscopic and histologic remission.

Measure: Sub-Study 3: Percentage of Participants with Mucosal Healing

Time: Through Week 300

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Description: Histologic remission per Geboes Score.

Measure: Sub-Study 3: Percentage of Participants with Histologic Remission

Time: Through Week 300

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Description: The UC-SQ is a patient questionnaire to assess severity of ulcerative colitis symptoms.

Measure: Sub-Study 3: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ)

Time: Week 0 to Week 300

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Description: Participants with an event that results in admission to the hospital.

Measure: Sub-Study 3: Percentage of Participants with Hospitalization

Time: Through Week 300

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Description: Participants who underwent surgery related to UC.

Measure: Sub-Study 3: Percentage of Participants with Ulcerative Colitis (UC)-Related Surgeries

Time: Through Week 300

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Description: The FACIT-Fatigue is a validated tool that measures an individual's level of fatigue during their usual daily activities over the past week.

Measure: Sub-Study 3: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Time: Week 0 to Week 300

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Description: The SF-36 is an indicator of overall health status.

Measure: Sub-Study 3: Change in 36-Item Short Form Health Status Survey (SF-36)

Time: Week 0 to Week 300

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Description: The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.

Measure: Sub-Study 3: Change in Inflammatory Bowel Disease Questionnaire (IBDQ)

Time: Through Week 300

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Description: The WPAI UC questionnaire was used to assess work and activity impairment due to symptoms of ulcerative colitis. The self-administered questionnaire measures the effect of the participant's health problems on work and daily activities in the previous week, specifically, the number of hours missed from work due to health problems, how much the subject's health problems affected work productivity, and how much the subject's health problems affected regular activities. Low scores indicate little or no impact of health problems on work and activities, and a negative change in the WPAI score indicates improvement.

Measure: Sub-Study 3: Change in Work Productivity and Impairment Questionnaire - UC (WPAI UC)

Time: Through Week 300

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Description: The European Quality of Life 5 Dimensions (EQ-5D-5L) is a standardized instrument used to measure health-related quality of life that can be used in a wide range of health conditions and treatments.

Measure: Sub-Study 3: Change in European Quality of Life 5 Dimensions (EQ-5D-5L)

Time: Through Week 300

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Description: The Rectal Bleeding Subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Rectal Bleeding Subscore indicates improvement.

Measure: Sub-Study 3: Change in RBS

Time: Through Week 300

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Description: The Stool Frequency Subscore ranges from 0 (normal) to 3 (severe disease). A negative change in Stool Frequency Subscore indicates improvement.

Measure: Sub-Study 3: Change in SFS

Time: Through Week 300

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Description: Stool samples were analyzed by a central laboratory for fecal calprotectin (FCP)qualitative measurement. Results are reported for participants in each category.

Measure: Sub-Study 3: Change in Fecal Calprotectin (FCP)

Time: Through Week 300

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Description: High sensitivity C-reactive protein was analyzed by a central laboratory. The median percent change from week 0 in CRP is assessed at each time point.

Measure: Sub-Study 3: Change in High Sensitivity C-reactive Protein (hs-CRP)

Time: Through Week 300

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Description: The PGIS is a response scale that describes the severity of the participants disease.

Measure: Sub-Study 3: Change in Patient Global Impression of Severity (PGIS)

Time: Week 0 to Week 300

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Description: The PGIC is a response scale. The participant will be asked by the Investigator or qualified designee to rate their change in their disease status.

Measure: Sub-Study 3: Change in Patient Global Impression of Change (PGIC) scores

Time: Through Week 300

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Description: Participants who discontinued corticosteroid use, in participants taking steroids at baseline (of induction).

Measure: Sub-Study 3: Percentage of Participants Who Discontinued Corticosteroid Use, in Participants Taking Steroids at Baseline (of Induction).

Time: Through Week 300

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Primary Outcomes

Description: Maximum observed plasma concentration (Cmax) of Midazolam

Measure: Maximum Observed Plasma Concentration (Cmax) of Midazolam

Time: Up to 71 Days

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Description: Time to maximum plasma concentration (Tmax) of Midazolam

Measure: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration

Measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Midazolam

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity

Measure: AUC From Time 0 to Infinity (AUCinf) of Midazolam

Time: Up to 71 Days

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Description: Terminal phase elimination rate constant (β) for Midazolam

Measure: Terminal Phase Elimination Rate Constant (β) of Midazolam

Time: Up to 71 Days

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Description: Terminal phase elimination half-life (t1/2) of Midazolam

Measure: Terminal Phase Elimination Half-Life (t1/2) of Midazolam

Time: Up to 71 Days

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Description: Maximum observed plasma concentration (Cmax) of Caffeine

Measure: Maximum Observed Plasma Concentration (Cmax) of Caffeine

Time: Up to 71 Days

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Description: Time to maximum plasma concentration (Tmax) of Caffeine

Measure: Time to Maximum Observed Plasma Concentration (Tmax) of Caffeine

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration

Measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Caffeine

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity

Measure: AUC From Time 0 to Infinity (AUCinf) of Caffeine

Time: Up to 71 Days

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Description: Terminal phase elimination rate constant (β) for Caffeine

Measure: Terminal Phase Elimination Rate Constant (β) of Caffeine

Time: Up to 71 Days

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Description: Terminal phase elimination half-life (t1/2) of Caffeine

Measure: Terminal Phase Elimination Half-Life (t1/2) of Caffeine

Time: Up to 71 Days

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Description: Maximum observed plasma concentration (Cmax) of Warfarin

Measure: Maximum Observed Plasma Concentration (Cmax) of Warfarin

Time: Up to 71 Days

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Description: Time to maximum plasma concentration (Tmax) of Warfarin

Measure: Time to Maximum Observed Plasma Concentration (Tmax) of Warfarin

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration

Measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Warfarin

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity

Measure: AUC From Time 0 to Infinity (AUCinf) of Warfarin

Time: Up to 71 Days

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Description: Terminal phase elimination rate constant (β) for Warfarin

Measure: Terminal Phase Elimination Rate Constant (β) of Warfarin

Time: Up to 71 Days

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Description: Terminal phase elimination half-life (t1/2) of Warfarin

Measure: Terminal Phase Elimination Half-Life (t1/2) of Warfarin

Time: Up to 71 Days

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Description: Maximum observed plasma concentration (Cmax) of Omeprazole

Measure: Maximum Observed Plasma Concentration (Cmax) of Omeprazole

Time: Up to 71 Days

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Description: Time to maximum plasma concentration (Tmax) of Omeprazole

Measure: Time to Maximum Observed Plasma Concentration (Tmax) of Omeprazole

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration

Measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Omeprazole

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity

Measure: AUC From Time 0 to Infinity (AUCinf) of Omeprazole

Time: Up to 71 Days

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Description: Terminal phase elimination rate constant (β) for Omeprazole

Measure: Terminal Phase Elimination Rate Constant (β) of Omeprazole

Time: Up to 71 Days

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Description: Terminal phase elimination half-life (t1/2) of Omeprazole

Measure: Terminal Phase Elimination Half-Life (t1/2) of Omeprazole

Time: Up to 71 Days

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Description: Maximum observed plasma concentration (Cmax) of Metoprolol

Measure: Maximum Observed Plasma Concentration (Cmax) of Metoprolol

Time: Up to 71 Days

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Description: Time to maximum plasma concentration (Tmax) of Metoprolol

Measure: Time to Maximum Observed Plasma Concentration (Tmax) of Metoprolol

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to time of the last measurable concentration

Measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time of the Last Measurable Concentration (AUCt) of Metoprolol

Time: Up to 71 Days

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Description: Area Under the Plasma Concentration-time Curve (AUC) from time 0 to infinity

Measure: AUC From Time 0 to Infinity (AUCinf) of Metoprolol

Time: Up to 71 Days

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Description: Terminal phase elimination rate constant (β) for Metoprolol

Measure: Terminal Phase Elimination Rate Constant (β) of Metoprolol

Time: Up to 71 Days

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Description: Terminal phase elimination half-life (t1/2) of Metoprolol

Measure: Terminal Phase Elimination Half-Life (t1/2) of Metoprolol

Time: Up to 71 Days

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Primary Outcomes

Description: The need for in-hospital colectomy or rescue therapy

Measure: Primary outcome measure: The need for in-hospital colectomy or rescue therapy

Time: 3 months

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Secondary Outcomes

Description: Duration and type/route of steroid use

Measure: 2.1: Duration and type/route of steroid use

Time: 3 months

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Description: 30 day colectomy free survival rates

Measure: 2.2: 30 day colectomy free survival rates

Time: 3 months

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Description: Covid-19 infection rates

Measure: 2.3: Covid-19 infection rates

Time: 3 months

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Description: Rate of Rescue therapy use

Measure: 2.4: Rate of Rescue therapy use

Time: 3 months

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Description: Duration of hospital stay

Measure: 2.5: Duration of hospital stay

Time: 3 months

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Description: Admission severity scoring

Measure: 2.6: Admission severity scoring

Time: 3 months

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Description: Readmission rates

Measure: 2.7: Readmission rates

Time: 3 months

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Primary Outcomes

Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Any AE occurring at or after the initial administration of study intervention through the day of last dose plus 30 days will be considered as TEAE.

Measure: Part 1, 2 and 3: Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability

Time: Up to 224 Days

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Description: Number of participants with vital sign abnormalities (temperature), pulse/heart rate, respiratory rate and blood pressure) will be reported.

Measure: Part 1, 2 and 3: Number of Participants with Vital Sign Abnormalities

Time: Up to 224 Days

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Description: Number of participants with physical examination abnormalities will be reported.

Measure: Part 1, 2 and 3: Number of Participants with Physical Examination Abnormalities

Time: Up to 224 Days

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Description: Number of participants with clinical laboratory abnormalities (serum chemistry, hematology and urinalysis) will be reported.

Measure: Part 1, 2 and 3: Number of Participants with Clinical Laboratory Abnormalities

Time: Up to 224 Days

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Description: Number of participants with ECG abnormalities will be reported.

Measure: Part 1, 2 and 3: Number of Participants with Electrocardiogram (ECG) Abnormalities

Time: Up to 224 Days

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Secondary Outcomes

Description: Plasma concentrations of JNJ-66525433 will be reported.

Measure: Part 1, 2 and 3: Plasma Concentrations of JNJ-66525433

Time: Up to 224 Days

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Description: Plasma concentrations of JNJ-66525433 after fasted or fed dosing will be reported.

Measure: Part 1: Plasma Concentrations of JNJ-66525433 After Fasted or Fed Dosing

Time: Up to Day 14

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Description: Mayo scoring system is used for assessment of ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each ranges from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12, where higher score indicates severe disease.

Measure: Part 3: Mayo Score

Time: Up to Day 84

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Description: Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease.

Measure: Part 3: Partial Mayo Score

Time: Up to Day 70

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Description: Endoscopy sub-score ranges from 0 to 3 where; 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = severe disease (spontaneous bleeding, ulceration).

Measure: Part 3: Endoscopic Subscore

Time: Up to Day 84

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Description: IBDQ18 is a validated, 32-item, self-reported questionnaire for participants with inflammatory bowel disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.

Measure: Part 3: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score

Time: Days 1, 7, 14, 28, 43, 70 and 84

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Description: Levels of mRNA knockdown will be reported to assess target engagement in biopsy tissue by dose level over time.

Measure: Part 2 and 3: Target Engagement of Messenger Ribonucleic Acid (mRNA) Levels

Time: Up to 182 Days

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Description: Tissue biopsy concentrations of JNJ-66525433 will be reported.

Measure: Part 2 and 3: Tissue Biopsy JNJ-66525433 Concentrations

Time: Up to 182 Days

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