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

• ClinicalTrials.gov Identifier: NCT06052059
• Recruitment Status: Recruiting
• First Posted: September 25, 2023
• Last Update Posted: November 24, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: PPD, Part of Thermo Fisher Scientific
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

The purpose of this protocol is to evaluate the efficacy and safety of MK-7240 in participants with moderately to severely active ulcerative colitis. Study 1's primary hypotheses are that at least 1 MK-7240 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 MK-7240 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 MK-7240 dose level is superior to Placebo in the proportion of participants achieving clinical remission per Modified Mayo Score at Week 12.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis	Drug: IV MK-7240; Drug: IV Placebo; Drug: SC MK-7240; Drug: SC Placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1020 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Induction and maintenance treatments will be blinded. Reinduction will not be blinded.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 18, 2023
• Estimated Primary Completion Date: November 21, 2026
• Estimated Study Completion Date: December 17, 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: Study 1: High Dose Induction, High Dose Maintenance; Participants receive high dose intravenous (IV) MK-7240, followed by a high dose subcutaneous (SC) MK-7240 regimen.	Drug: IV MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously; Other Name: PRA023; Drug: SC MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously; Other Name: PRA023
Experimental: Study 1: High Dose Induction, Low Dose Maintenance; Participants receive high dose IV MK-7240, followed by a low dose SC MK-7240 regimen.	Drug: IV MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously; Other Name: PRA023; Drug: SC MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously; Other Name: PRA023; Drug: SC Placebo; Placebo matching SC MK-7240
Experimental: Study 1: Low Dose Induction, Low Dose Maintenance; Participants receive low dose IV MK-7240, followed by a low dose SC MK-7240 regimen.	Drug: IV MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously; Other Name: PRA023; Drug: SC MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously; Other Name: PRA023; Drug: SC Placebo; Placebo matching SC MK-7240
Placebo Comparator: Study 1: Placebo; Participants receive IV placebo, followed by an SC placebo regimen.	Drug: IV MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously; Other Name: PRA023; Drug: IV Placebo; Placebo matching IV MK-7240; Drug: SC Placebo; Placebo matching SC MK-7240
Experimental: Study 1: High Dose Extension; Participants receive a high dose SC MK-7240 regimen. Participants may be enrolled in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.	Drug: SC MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously; Other Name: PRA023
Experimental: Study 1: Low Dose Extension; Participants receive a low dose SC MK-7240 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 MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously; Other Name: PRA023; Drug: SC Placebo; Placebo matching SC MK-7240
Experimental: Study 2: High Dose Induction; Participants receive high dose IV MK-7240.	Drug: IV MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously; Other Name: PRA023
Experimental: Study 2: Low Dose Induction; Participants receive low dose IV MK-7240.	Drug: IV MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously; Other Name: PRA023
Placebo Comparator: Study 2: Placebo; 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 MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously; Other Name: PRA023; Drug: IV Placebo; Placebo matching IV MK-7240; Drug: SC Placebo; Placebo matching SC MK-7240
Experimental: Study 2: High Dose Extension; Participants receive a high dose SC MK-7240 regimen. Participants may be enrolled in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.	Drug: SC MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously; Other Name: PRA023
Experimental: Study 2: Low Dose Extension; Participants receive a low dose SC MK-7240 regimen. Participants may be enrolled in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.	Drug: SC MK-7240; Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously; Other Name: PRA023; Drug: SC Placebo; Placebo matching SC MK-7240

Outcome Measures

Primary Outcome Measures :

1. Study 1: Percentage of Participants Achieving Clinical Remission Per Modified Mayo Score (MMS) at Week 12 [ Time Frame: Week 12 ]
   The Modified Mayo Score (MMS) is a composite score of ulcerative colitis (UC) disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: Endoscopic subscore (ES), scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); Stool frequency subscore (SFS), scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and rectal bleeding subscore (RBS), scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
2. Study 1: Percentage of Participants Achieving Clinical Remission Per MMS at Week 52 [ Time Frame: Week 52 ]
   The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
3. Study 1: Percentage of Participants With One or More Adverse Events (AEs) [ Time Frame: Up to approximately 52 weeks ]
   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience an AE will be reported.
4. Study 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE [ Time Frame: Up to approximately 52 weeks ]
   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
5. Study 2: Percentage of Participants Achieving Clinical Remission Per MMS at Week 12 [ Time Frame: Week 12 ]
   The MMS is a composite score of UC disease activity on a scale of increasing severity from 0-9, calculated by summing three subscores: ES, scored on a scale of increasing severity from 0 (normal or inactive disease) to 3 (severe disease, such as spontaneous bleeding or ulceration); SFS, scored on a scale of increasing frequency from 0 (normal number of stools) to 3 (≥5 stools more than normal per day for the participant); and RBS, scored on a scale of increasing severity from 0 (no blood seen) to 3 (blood alone passed). Clinical Remission is defined as an ES of 0 or 1, RBS of 0, and SFS of 0 or 1 and not greater than the baseline SFS.
6. Study 2: Percentage of Participants With One or More AEs [ Time Frame: Up to approximately 12 weeks ]
   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.
7. Study 2: Percentage of Participants Who Discontinued Study Intervention Due to an AE [ Time Frame: Up to approximately 12 weeks ]
   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 MK-7240 or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody

Contacts and Locations

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

Locations

United States, Alabama

Digestive Health Specialists ( Site 0135); Recruiting

Dothan, Alabama, United States, 36301

Contact: Study Coordinator 334-836-1212

United States, Arizona

GI Alliance - Sun City ( Site 0103); Recruiting

Sun City, Arizona, United States, 85351

Contact: Study Coordinator 000-000-0000

United States, Colorado

Peak Gastroenterology Associates ( Site 0116); Recruiting

Colorado Springs, Colorado, United States, 80907

Contact: Study Coordinator 719-663-8590

United States, Illinois

GI Alliance - Glenview ( Site 0168); Recruiting

Glenview, Illinois, United States, 60026

Contact: Study Coordinator 773-450-7222

GI ALLIANCE - GURNEE ( Site 0107); Recruiting

Gurnee, Illinois, United States, 60031

Contact: Study Coordinator 000-000-0000

United States, Michigan

Clinical Research Institute of Michigan, LLC ( Site 0108); Recruiting

Chesterfield, Michigan, United States, 48047

Contact: Study Coordinator 586-598-5731

Clinical Research Institute of Michigan, LLC ( Site 0150); Recruiting

Troy, Michigan, United States, 48098

Contact: Study Coordinator 586-202-0600

United States, New York

New York Gastroenterology Associates ( Site 0159); Recruiting

New York, New York, United States, 10128

Contact: Study Coordinator 212-369-2490

United States, Texas

CARTA - Clinical Associates In Research Therapeutics Of America ( Site 0122); Recruiting

San Antonio, Texas, United States, 78212

Contact: Study Coordinator 210-444-9363

Southern Star Research Institute ( Site 0106); Recruiting

San Antonio, Texas, United States, 78229

Contact: Study Coordinator 210-581-2812

GI Alliance - Southlake ( Site 0104); Recruiting

Southlake, Texas, United States, 76092-9167

Contact: Study Coordinator 817-424-1525

Tyler Research Institute ( Site 0105); Recruiting

Tyler, Texas, United States, 75701

Contact: Study Coordinator 903-630-6211

Texas Digestive Disease Consultants ( Site 0136); Recruiting

Webster, Texas, United States, 77598

Contact: Study Coordinator 281-480-6264

United States, Utah

Velocity Clinical Research, Salt Lake City ( Site 3801); Recruiting

West Jordan, Utah, United States, 84088

Contact: Study Coordinator 801-542-8190

United States, Washington

Washington Gastroenterology - Tacoma ( Site 0102); Recruiting

Tacoma, Washington, United States, 98405

Contact: Study Coordinator 111-111-1111

Sponsors and Collaborators

Merck Sharp & Dohme LLC

PPD, Part of Thermo Fisher Scientific

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

More Information

Additional Information:

Merck Clinical Trials Information 

Plain Language Summary 

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT06052059
• Other Study ID Numbers: 7240-001; PR200-301 ( Other Identifier: PrometheusBio )
• First Posted: September 25, 2023
• Last Update Posted: November 24, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Merck Sharp & Dohme LLC:

Inflammatory Bowel Disease

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases