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

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06052059
• Other study ID #: 7240-001
• Secondary ID: PR200-301jRCT203
• Status: Recruiting
• Phase: Phase 3
• Start date: October 25, 2023
• Est. completion date: December 17, 2029

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1020
• Est. completion date: December 17, 2029
• Est. primary completion date: November 21, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• IV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
• IV Placebo
Placebo matching IV tulisokibart
• SC Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
• SC Placebo
Placebo matching SC tulisokibart

Locations

Country	Name	City	State
Canada	Toronto Immune & Digestive Health Institute ( Site 0005)	Toronto	Ontario
Chile	Clínica MEDS La Dehesa ( Site 2207)	Lo Barnechea	Region M. De Santiago
Chile	CECIM ( Site 2200)	Santiago	Region M. De Santiago
Chile	Centro de Estudios Clínicos SAGA-CECSAGA ( Site 2203)	Santiago	Region M. De Santiago
Chile	Clínica Universidad de Los Andes ( Site 2202)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 2208)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile-CICUC ( Site 2205)	Santiago	Region M. De Santiago
Chile	Clinical Research Chile SpA ( Site 2201)	Valdivia	Los Rios
Dominican Republic	CEMDOE - Centro Médico de Diabetes, Obesidad y Especialidades ( Site 3601)	Santo Domingo	Distrito Nacional
Israel	Bnai Zion Medical Center ( Site 1103)	Haifa
Israel	Rambam Health Care Campus ( Site 1101)	Haifa
Israel	Edith Wolfson Medical Center ( Site 1104)	Holon
Israel	Shaare Zedek Medical Center ( Site 1108)	Jerusalem
Israel	Rabin Medical Center ( Site 1107)	Petah Tikva
Israel	Sheba Medical Center ( Site 1100)	Ramat Gan
Japan	Asahikawa City Hospital ( Site 2840)	Asahikawa	Hokkaido
Japan	Asahikawa Medical College Hospital ( Site 2815)	Asahikawa	Hokkaido
Japan	Ginza Central Clinic ( Site 2824)	Chuo	Tokyo
Japan	Sai Gastroenterology/Proctology Clinic ( Site 2814)	Fujiidera	Osaka
Japan	Fukuoka University Hospital ( Site 2818)	Fukuoka
Japan	National Hospital Organization Fukuyama Medical Center ( Site 2831)	Fukuyama	Hiroshima
Japan	Matsuda Hospital ( Site 2826)	Hamamatsu	Shizuoka
Japan	Kansai Medical University Hospital ( Site 2823)	Hirakata	Osaka
Japan	Kagoshima IBD Gastroenterology Clinic ( Site 2821)	Kagoshima
Japan	Gokeikai Ofuna Chuo Hospital ( Site 2801)	Kamakura	Kanagawa
Japan	Ishikawa Prefectural Central Hospital ( Site 2835)	Kanazawa	Ishikawa
Japan	Tsujinaka Hospital - Kashiwanoha ( Site 2802)	Kashiwa	Chiba
Japan	Yamanashi Prefectural Central Hospital ( Site 2836)	Kofu	Yamanashi
Japan	National Hospital Organization Kyoto Medical Center ( Site 2813)	Kyoto
Japan	Iwate Medical University Uchimaru Medical Center ( Site 2833)	Morioka	Iwate
Japan	Hyogo Medical University Hospital ( Site 2830)	Nishinomiya	Hyogo
Japan	Ishida Clinic of IBD and Gastroenterology ( Site 2820)	Oita
Japan	Infusion Clinic ( Site 2806)	Osaka
Japan	Saga University Hospital ( Site 2812)	Saga
Japan	Tokitokai Tokito Clinic Coloproctology Center ( Site 2811)	Saitama
Japan	Toho University Sakura Medical Center ( Site 2805)	Sakura	Chiba
Japan	Medical Corporation Sapporo IBD Clinic ( Site 2842)	Sapporo	Hokkaido
Japan	Sapporo Tokushukai Hospital ( Site 2808)	Sapporo	Hokkaido
Japan	Shizuoka Medical Center ( Site 2837)	Shimizu	Shizuoka
Japan	The Jikei University Hospital ( Site 2843)	Tokyo
Japan	Tokyo Yamate Medical Center ( Site 2803)	Tokyo
Japan	Toyama Prefectural Central Hospital ( Site 2807)	Toyama
Japan	Mie University Hospital ( Site 2838)	Tsu	Mie
Korea, Republic of	Dong-A University Hospital ( Site 3010)	Busan	Pusan-Kwangyokshi
Korea, Republic of	Yeungnam Univeristy Medical Center ( Site 3004)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	The Catholic University of Korea, Daejeon St. Mary's Hospital ( Site 3011)	Daejeon	Taejon-Kwangyokshi
Korea, Republic of	Chung-Ang University Hospital ( Site 3008)	Dongjak-gu	Seoul
Korea, Republic of	Inje University Haeundae Paik Hospital ( Site 3009)	Haeundae-gu	Pusan-Kwangyokshi
Korea, Republic of	Asan Medical Center ( Site 3007)	Seoul
Korea, Republic of	Kangbuk Samsung Hospital-Internal Medicine ( Site 3002)	Seoul
Korea, Republic of	Kyung Hee University Hospital ( Site 3013)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 3001)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 3005)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System-Department of Internal Medicine ( Site 3000)	Seoul
Korea, Republic of	The Catholic University of Korea, Eunpyeong St. Mary's Hospital ( Site 3012)	Seoul
Korea, Republic of	The Catholic University Of Korea St. Vincent's Hospital-Gastroenterology ( Site 3006)	Suwon-si	Kyonggi-do
Korea, Republic of	Wonju Severance Christian Hospital-Internal Medicine ( Site 3003)	Wonju	Kang-won-do
Netherlands	Radboudumc ( Site 1402)	Nijmegen	Gelderland
Switzerland	INTESTO-Gastroenterologische Praxis / Crohn-Colitis Zentrum Bern ( Site 1902)	Bern	Berne
Switzerland	Cantonal Hospital St.Gallen-Klinik für Gastroenterologie / Hepatologie ( Site 1901)	st.Gallen	Sankt Gallen
Switzerland	UniversitätsSpital Zürich-Gastroenterologie & Hepatologie ( Site 1900)	Zürich	Zurich
United States	University of Michigan ( Site 0143)	Ann Arbor	Michigan
United States	Atlanta Gastroenterology Associates - Peachtree Dunwoody ( Site 0115)	Atlanta	Georgia
United States	Baton Rouge General Medical Center - Bluebonnet ( Site 0112)	Baton Rouge	Louisiana
United States	Connecticut Clinical Research Institute ( Site 0126)	Bristol	Connecticut
United States	Gastroenterology Consultants of Clearwater ( Site 0152)	Clearwater	Florida
United States	Clinical Research Institute of Michigan, LLC ( Site 0108)	Clinton Township	Michigan
United States	Iowa Digestive Disease Center ( Site 0123)	Clive	Iowa
United States	Peak Gastroenterology Associates ( Site 0116)	Colorado Springs	Colorado
United States	Atlanta Center for Gastroenterology ( Site 0155)	Decatur	Georgia
United States	Digestive Health Specialists ( Site 0135)	Dothan	Alabama
United States	IMC-Gulf Coast Gastroenterology ( Site 0157)	Fairhope	Alabama
United States	GI Alliance - Garland ( Site 0109)	Garland	Texas
United States	GI Alliance - Glenview ( Site 0168)	Glenview	Illinois
United States	Carolina Digestive Diseases and Endoscopy Center ( Site 3809)	Greenville	North Carolina
United States	GI ALLIANCE - GURNEE ( Site 0107)	Gurnee	Illinois
United States	Clinical Trial Network ( Site 3819)	Houston	Texas
United States	Nature Coast Clinical Research - Inverness ( Site 3806)	Inverness	Florida
United States	Research Solutions of Arizona ( Site 3816)	Litchfield Park	Arizona
United States	GI Alliance - Lubbock ( Site 0167)	Lubbock	Texas
United States	GI Alliance: Mansfield ( Site 0161)	Mansfield	Texas
United States	Circuit Clinical /Middletown Medical PC ( Site 3831)	Middletown	New York
United States	Quality Medical Research ( Site 3807)	Nashville	Tennessee
United States	New York Gastroenterology Associates ( Site 0159)	New York	New York
United States	Clinnova Research - Orange ( Site 3803)	Orange	California
United States	Gastroenterology Associates of Orangeburg ( Site 0149)	Orangeburg	South Carolina
United States	University Gastroenterology ( Site 0164)	Providence	Rhode Island
United States	CARTA - Clinical Associates In Research Therapeutics Of America ( Site 0122)	San Antonio	Texas
United States	Southern Star Research Institute ( Site 0106)	San Antonio	Texas
United States	GI Alliance - San Marcos ( Site 0130)	San Marcos	Texas
United States	GI Alliance - Southlake ( Site 0104)	Southlake	Texas
United States	GI Alliance - Sun City ( Site 0103)	Sun City	Arizona
United States	Washington Gastroenterology - Tacoma ( Site 0102)	Tacoma	Washington
United States	Clinical Research Institute of Michigan, LLC ( Site 0150)	Troy	Michigan
United States	Tyler Research Institute ( Site 0105)	Tyler	Texas
United States	Texas Digestive Disease Consultants ( Site 0136)	Webster	Texas
United States	Velocity Clinical Research, Salt Lake City ( Site 3801)	West Jordan	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	PPD, Part of Thermo Fisher Scientific

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Dominican Republic,  Israel,  Japan,  Korea, Republic of,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Study 1: 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
Secondary	Study 1: 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary