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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06052059
Recruitment Status : Recruiting
First Posted : September 25, 2023
Last Update Posted : April 11, 2024
Sponsor:
Collaborator:
PPD, Part of Thermo Fisher Scientific
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: IV Tulisokibart Drug: IV Placebo Drug: SC Tulisokibart 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.

Layout table for study information
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 25, 2023
Estimated Primary Completion Date : November 21, 2026
Estimated Study Completion Date : December 17, 2029

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Study 1: High Dose Induction, High Dose Maintenance
Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.
Drug: IV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
Other Names:
  • PRA023
  • MK-7240

Drug: SC Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
Other Names:
  • PRA023
  • MK-7240

Experimental: Study 1: High Dose Induction, Low Dose Maintenance
Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Drug: IV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
Other Names:
  • PRA023
  • MK-7240

Drug: SC Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
Other Names:
  • PRA023
  • MK-7240

Drug: SC Placebo
Placebo matching SC tulisokibart

Experimental: Study 1: Low Dose Induction, Low Dose Maintenance
Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Drug: IV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
Other Names:
  • PRA023
  • MK-7240

Drug: SC Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
Other Names:
  • PRA023
  • MK-7240

Drug: SC Placebo
Placebo matching SC tulisokibart

Placebo Comparator: Study 1: Placebo
Participants receive IV placebo, followed by an SC placebo regimen.
Drug: IV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
Other Names:
  • PRA023
  • MK-7240

Drug: IV Placebo
Placebo matching IV tulisokibart

Drug: SC Placebo
Placebo matching SC tulisokibart

Experimental: Study 1: High Dose Extension
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
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
Other Names:
  • PRA023
  • MK-7240

Experimental: Study 1: Low Dose Extension
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
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
Other Names:
  • PRA023
  • MK-7240

Drug: SC Placebo
Placebo matching SC tulisokibart

Experimental: Study 2: High Dose Induction
Participants receive high dose IV tulisokibart.
Drug: IV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
Other Names:
  • PRA023
  • MK-7240

Experimental: Study 2: Low Dose Induction
Participants receive low dose IV tulisokibart.
Drug: IV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
Other Names:
  • PRA023
  • MK-7240

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 Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
Other Names:
  • PRA023
  • MK-7240

Drug: IV Placebo
Placebo matching IV tulisokibart

Drug: SC Placebo
Placebo matching SC tulisokibart

Experimental: Study 2: High Dose Extension
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
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
Other Names:
  • PRA023
  • MK-7240

Experimental: Study 2: Low Dose Extension
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
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered subcutaneously
Other Names:
  • PRA023
  • MK-7240

Drug: SC Placebo
Placebo matching SC tulisokibart




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 tulisokibart or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06052059


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

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
PPD, Part of Thermo Fisher Scientific
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
Additional Information:
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT06052059    
Other Study ID Numbers: 7240-001
PR200-301 ( Other Identifier: PrometheusBio )
jRCT2031230563 ( Registry Identifier: jRCT )
First Posted: September 25, 2023    Key Record Dates
Last Update Posted: April 11, 2024
Last Verified: April 2024
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

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