A Study to Evaluate Efficacy and Safety of Tulisokibart (MK-7240) in Participants With Moderately to Severely Active Ulcerative Colitis (MK-7240-001)

Study Overview
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Brief Summary
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The purpose of this protocol is to evaluate the efficacy and safety of tulisokibart in participants with moderately to severely active ulcerative colitis. Study 1's primary hypotheses are that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission per Modified Mayo Score at Week 12, and that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission per Modified Mayo Score at week 52. Study 2's primary hypothesis is that at least 1 tulisokibart dose level is superior to Placebo in the proportion of participants achieving clinical remission per Modified Mayo Score at Week 12.

Detailed Description
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The protocol consists of 2 studies. Study 1 includes induction and maintenance treatment, and Study 2 includes only induction treatment. Each study has its own hypotheses and outcome measures that will be assessed independently.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Induction and Maintenance Study to Evaluate the Efficacy and Safety of PRA023 in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: IV Tulisokibart
* Drug: IV Placebo
* Drug: SC Tulisokibart
* Drug: SC Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has had ulcerative colitis (UC) (from onset of symptoms) for at least 3 months before randomization Has moderately to severely active UC Weight ≥40 kg Satisfies at least 1 of the following criteria: Has had an inadequate response or loss of response to 1 or more protocol-specified UC treatments Protocol specified corticosteroid dependence Has been intolerant to 1 or more protocol-specified UC treatments Is on treatment with any protocol-specified drugs during the study and meets drug stabilization requirements, as applicable Adolescent participants ≥16 and <18 years of age can participate if approved by the country or regulatory/health authority Participant assigned male sex at birth, if capable of producing sperm, agrees to abstain from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent; or uses prescribed contraception unless azoospermic A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding and Is not a participant of childbearing potential (POCBP); or is a POCBP and uses an acceptable contraceptive method, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention, medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy Exclusion Criteria: Has a diagnosis of Crohn's Disease (CD) or indeterminate colitis (inflammatory bowel disease (IBD)-undefined) or other types of colitis or enteritis that may confound efficacy assessment. Has a current diagnosis of fulminant colitis and/or toxic megacolon Has UC limited to the rectum (i.e, must have evidence of UC extending beyond the rectosigmoid junction, which is  10 cm from the anal margin) Has a current or impending need for colostomy or ileostomy Has had a total proctocolectomy or partial colectomy Has received fecal microbial transplantation within 4 weeks before randomization Has been hospitalized for the treatment of UC within 2 weeks before screening Has prior or current evidence of definite low-grade or high-grade colonic dysplasia including dysplasia identified during the Screening colonoscopy that has not been completely removed Has any active or serious infections without resolution after adequate treatment Has had a herpes zoster reactivation or cytomegalovirus that resolved less than 8 weeks before screening Has a transplanted organ which requires continued immunosuppression Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) within the last 5 years Is known to be infected with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidelines), or inadequately treated TB (for participants with history of TB) Has confirmed or suspected COVID-19 infection Has a history of drug or alcohol abuse within 6 months prior to screening Has had major surgery within 3 months before screening or has a major surgery (i.e, requiring general anesthesia) planned during the study Is currently receiving or is planning to receive total parenteral nutrition at any time during study treatment Has received UC-related antibiotics and has not been on stable doses for at least 14 days before randomization or has discontinued these medications within 14 days of randomization Requires treatment with a therapy that does not adhere to the protocol-specified guidance parameters Has received protocol-specified prohibited medications Has had prior exposure to tulisokibart or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study 1: High Dose Induction, High Dose Maintenance<br>Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen. | Drug: IV Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously<br>* Other names: MK-7240;Drug: SC Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously<br>* Other names: MK-7240;|
| Experimental: Study 1: High Dose Induction, Low Dose Maintenance<br>Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen. | Drug: IV Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously<br>* Other names: MK-7240;Drug: SC Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously<br>* Other names: MK-7240;Drug: SC Placebo<br>* Placebo matching SC tulisokibart<br>|
| Experimental: Study 1: Low Dose Induction, Low Dose Maintenance<br>Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen. | Drug: IV Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously<br>* Other names: MK-7240;Drug: SC Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously<br>* Other names: MK-7240;Drug: SC Placebo<br>* Placebo matching SC tulisokibart<br>|
| Placebo Comparator: Study 1: Placebo<br>Participants receive IV placebo, followed by an SC placebo regimen. | Drug: IV Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously<br>* Other names: MK-7240;Drug: IV Placebo<br>* Placebo matching IV tulisokibart<br>Drug: SC Placebo<br>* Placebo matching SC tulisokibart<br>|
| Experimental: Study 1: High Dose Extension<br>Participants receive a high dose SC tulisokibart regimen. Participants may be enrolled in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites. | Drug: SC Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously<br>* Other names: MK-7240;|
| Experimental: Study 1: Low Dose Extension<br>Participants receive a low dose SC tulisokibart and placebo regimen. Participants may be enrolled in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites. | Drug: SC Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously<br>* Other names: MK-7240;Drug: SC Placebo<br>* Placebo matching SC tulisokibart<br>|
| Experimental: Study 2: High Dose Induction<br>Participants receive high dose IV tulisokibart. | Drug: IV Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously<br>* Other names: MK-7240;|
| Experimental: Study 2: Low Dose Induction<br>Participants receive low dose IV tulisokibart. | Drug: IV Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously<br>* Other names: MK-7240;|
| Placebo Comparator: Study 2: Placebo<br>Participants receive IV placebo. Participants who meet protocol-specified conditions may later enter either the Study 2: High Dose Extension arm or Study 2: Low Dose Extension arm. | Drug: IV Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously<br>* Other names: MK-7240;Drug: IV Placebo<br>* Placebo matching IV tulisokibart<br>Drug: SC Placebo<br>* Placebo matching SC tulisokibart<br>|
| Experimental: Study 2: High Dose Extension<br>Participants receive a high dose SC tulisokibart regimen. Participants may be enrolled in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites. | Drug: SC Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously<br>* Other names: MK-7240;|
| Experimental: Study 2: Low Dose Extension<br>Participants receive a low dose SC tulisokibart regimen. Participants may be enrolled in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites. | Drug: SC Tulisokibart<br>* Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously<br>* Other names: MK-7240;Drug: SC Placebo<br>* Placebo matching SC tulisokibart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study 1: Percentage of Participants Achieving Clinical Remission Per Modified Mayo Score (MMS) at 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. | Week 12 | 
| Study 1: Percentage of Participants Achieving Clinical Remission Per MMS at 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. | Week 52 | 
| Study 1: Percentage of Participants With One or More Adverse Events (AEs) | 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. | Up to approximately 52 weeks | 
| Study 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE | 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. | Up to approximately 52 weeks | 
| Study 2: Percentage of Participants Achieving Clinical Remission Per MMS at 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. | Week 12 | 
| Study 2: Percentage of Participants With One or More AEs | 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. | Up to approximately 12 weeks | 
| Study 2: Percentage of Participants Who Discontinued Study Intervention Due to an AE | 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. | Up to approximately 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study 1: Percentage of Participants Achieving Clinical Response Per Partial Modified Mayo Score (pMMS) at 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. | Week 2 | 
| Study 1: Percentage of Participants With Endoscopic Improvement at 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. | Week 12 | 
| Study 1: Percentage of Participants Achieving a Clinical Response Per MMS at 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. | Week 12 | 
| Study 1: Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement (HEMI) at 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). | Week 12 | 
| Study 1: Percentage of Participants Achieving Clinical Remission Per pMMS at 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. | Week 12 | 
| Study 1: Percentage of Participants With Endoscopic Remission at 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. | Week 12 | 
| Study 1: Percentage of Participants Reporting No Bowel Urgency at 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. | Week 12 | 
| Study 1: Percentage of Participants Reporting No Abdominal Pain at 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. | Week 12 | 
| Study 1: Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at 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. | Week 12 | 
| Study 1: Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at 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. | Baseline and Week 12 | 
| Percentage of Diagnostic Assay Positive (Dx+) Participants Achieving Clinical Remission Per MMS at 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. | Week 12 | 
| Percentage of Dx+ Participants With Endoscopic Improvement at 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. | Week 12 | 
| Study 1: Percentage of Participants Achieving Histologic-Endoscopic Remission (HER) at 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). | Week 12 | 
| Study 1: Percentage of Participants with Endoscopic Improvement at 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. | Week 52 | 
| Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission Per MMS at 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. | Week 52 | 
| Study 1: Percentage of Participants Achieving HEMI at 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). | Week 52 | 
| Study 1: Percentage of Participants Achieving Clinical Remission Per pMMS at 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. | Week 52 | 
| Study 1: Percentage of Participants Achieving Sustained Clinical Remission Per MMS at Both 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. | Week 12 and Week 52 | 
| Study 1: Percentage of Participants Reporting No Bowel Urgency at 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. | Week 52 | 
| Study 1: Percentage of Participants Reporting No Abdominal Pain at 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. | Week 52 | 
| Study 1: Percentage of Participants With Endoscopic Remission at 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. | Week 52 | 
| Study 1: Percentage of Participants with Sustained Clinical Response Per MMS at Both 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. | Week 12, and Week 52 | 
| Study 1: Percentage of Participants with Sustained Endoscopic Improvement at Both 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. | Week 12 and Week 52 | 
| Study 1: Percentage of Participants Achieving HER at 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). | Week 52 | 
| Study 1: Percentage of Participants Achieving IBDQ Remission at 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. | Week 52 | 
| Study 1: Change from Baseline in FACIT-Fatigue Score at 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. | Baseline and Week 52 | 
| Percentage of Dx+ Participants Achieving Clinical Remission Per MMS at 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. | Week 52 | 
| Percentage of Dx+ Participants With Endoscopic Improvement at 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. | Week 52 | 
| Study 2: Percentage of Participants with Clinical Response Per pMMS at 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. | Week 2 | 
| Study 2: Percentage of Participants With Endoscopic Improvement at 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. | Week 12 | 
| Study 2: Percentage of Participants Achieving a Clinical Response Per MMS at 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. | Week 12 | 
| Study 2: Percentage of Participants Achieving HEMI at 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). | Week 12 | 
| Study 2: Percentage of Participants Achieving Clinical Remission Per pMMS at 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. | Week 12 | 
| Study 2: Percentage of Participants With Endoscopic Remission at 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. | Week 12 | 
| Study 2: Percentage of Participants Reporting No Bowel Urgency at Week 12 | Bowel urgency is measured using a numeric rating scale (NRS), which rates bowel urgency on a 0-11 scale of increasing severity. | Week 12 | 
| Study 2: Percentage of Participants Reporting No Abdominal Pain at 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. | Week 12 | 
| Study 2: Percentage of Participants Achieving IBDQ Remission at 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. | Week 12 | 
| Study 2: Change from Baseline in FACIT-Fatigue Score at 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. | Baseline and Week 12 | 
| Study 2: Percentage of Participants Achieving HER at 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. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease