A Study to Evaluate the Efficacy and Safety of Tulisokibart (MK-7240) in Participants With Moderate to Severe Crohn's Disease (MK-7240-008)

Phase 3

Recruiting

• Conditions: Crohn's Disease
• Interventions: Drug: IV Tulisokibart; Drug: SC Tulisokibart; Other: IV Placebo; Other: SC Placebo

• Registration Number: NCT06430801
• Lead Sponsor: 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 Crohn's disease. 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 Crohn's Disease Activity Index score (\<150, US/FDA) or per stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 52 (US/FDA and EU/EMA), and that at least 1 tulisokibart dose level is superior to placebo in the proportion of participants achieving clinical remission per Crohn's Disease Activity Index score (\<150, US/FDA) or per stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 12 (US/FDA and EU/EMA). 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 Crohn's Disease Activity Index score (\<150, US/FDA) or stool frequency and abdominal pain score (EU/EMA) and in the proportion of participants achieving endoscopic response at Week 12 (US/FDA and EU/EMA).

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 Timeline

• Study First Submitted: 2024-05-21
• Study First Submitted QC: 2024-05-21
• Study First Posted: 2024-05-28
• Study Start: 2024-06-05
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-17
• Last Update Posted: 2025-09-18
• Primary Completion: 2028-10-30
• Study Completion: 2029-11-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

• Has had a diagnosis of CD at least 3 months before study.
• Has moderately to severely active CD.
• Demonstrated inadequate response, loss of response, or intolerance to one or more of the following categories of drugs: oral locally acting steroids, systemic steroids, immunomodulators, biologic and/or small molecule advanced therapies.
• Adolescent participants ≥16 and <18 years of age can participate if approved by the country or regulatory/health authority.

Exclusion Criteria

• Has diagnosis of ulcerative colitis (UC) or indeterminate colitis.
• Has CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or ileal involvement.
• Currently has any of the following complications of CD: suspected or diagnosed with intra-abdominal or perianal abscess, known symptomatic stricture or colonic stenosis not passable in endoscopy, fulminant colitis, toxic megacolon, or any other manifestation that might require surgery while enrolled in the study.
• Has current stoma or need for colostomy or ileostomy.
• Is missing >2 segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum.
• Has been diagnosed with short gut or short bowel syndrome, or any other uncontrolled chronic diarrhea besides Crohn's disease.
• Has surgical bowel resection within 3 months of study.
• Has prior or current gastrointestinal dysplasia.
• Has chronic infection requiring ongoing antimicrobial treatment.
• Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) and is disease free for <5 years.
• Is infected with Hepatitis B virus (HBV), Hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• Has active tuberculosis.
• Has confirmed or suspected coronavirus disease of 2019 (COVID-19) infection.
• Prior exposure to tulisokibart (MK-7240, PRA023) or another anti-TL1A antibody.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study 1: High Dose Induction, High Dose Maintenance	IV Tulisokibart	Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.
Study 1: High Dose Induction, High Dose Maintenance	SC Tulisokibart	Participants receive high dose intravenous (IV) tulisokibart, followed by a high dose subcutaneous (SC) tulisokibart regimen.
Study 1: High Dose Induction, Low Dose Maintenance	IV Tulisokibart	Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Study 1: High Dose Induction, Low Dose Maintenance	SC Tulisokibart	Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Study 1: High Dose Induction, Low Dose Maintenance	SC Placebo	Participants receive high dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Study 1: Low Dose Induction, Low Dose Maintenance	IV Tulisokibart	Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Study 1: Low Dose Induction, Low Dose Maintenance	SC Tulisokibart	Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Study 1: Low Dose Induction, Low Dose Maintenance	SC Placebo	Participants receive low dose IV tulisokibart, followed by a low dose SC tulisokibart regimen.
Study 1: Placebo	IV Tulisokibart	Participants receive IV placebo, followed by an SC placebo regimen.
Study 1: Placebo	IV Placebo	Participants receive IV placebo, followed by an SC placebo regimen.
Study 1: Placebo	SC Placebo	Participants receive IV placebo, followed by an SC placebo regimen.
Study 1: High Dose Extension	SC Tulisokibart	Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
Study 1: Low Dose Extension	SC Tulisokibart	Participants receive a low dose SC tulisokibart and placebo regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
Study 1: Low Dose Extension	SC Placebo	Participants receive a low dose SC tulisokibart and placebo regimen. Participants may continue in this arm after completing participation in their original arm, if they meet protocol-specific prerequisites.
Study 2: High Dose Induction	IV Tulisokibart	Participants receive high dose IV tulisokibart.
Study 2: Low Dose Induction	IV Tulisokibart	Participants receive low dose IV tulisokibart.
Study 2: Low Dose Induction	SC Placebo	Participants receive low dose IV tulisokibart.
Study 2: Placebo	IV Tulisokibart	Participants receive IV placebo.
Study 2: Placebo	IV Placebo	Participants receive IV placebo.
Study 2: Placebo	SC Placebo	Participants receive IV placebo.
Study 2: High Dose Extension	SC Tulisokibart	Participants receive a high dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.
Study 2: Low Dose Extension	SC Tulisokibart	Participants receive a low dose SC tulisokibart regimen. Participants may continue in this arm only after completing participation in their original arm, if they meet protocol-specific prerequisites.

Primary Outcome Measures

Name	Time	Method
Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52	Week 52	The percentage of participants achieving clinical remission per stool frequency/abdominal pain score (SF/APS), as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 1 will be presented.
Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12	Week 12	The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 1 will be presented.
Study 1: Percentage of Participants Achieving Endoscopic Response at Week 12	Week 12	The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in SES-CD from baseline for study 1 will be presented.
Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 2 will be presented.
Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12	Week 12	The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 2 will be presented.
Study 2: Percentage of Participants Achieving Endoscopic Response at Week 12	Week 12	The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in SES-CD from baseline for study 2 will be presented.
Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Crohn's Disease Activity Index (CDAI) Score at Week 52	Week 52	The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
Study 1: Percentage of Participants Achieving Endoscopic Response at Week 52	Week 52	The percentage of participants achieving endoscopic response, as defined by a ≥50% decrease in Simplified endoscopic score for Crohn's disease (SES-CD) from baseline for study 1 will be presented.

Secondary Outcome Measures

Name	Time	Method
Study 1: Percentage of Participants Who Experienced an Adverse Event (AE)	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 for study 1 will be presented.
Study 1: Percentage of Participants who Discontinue Study Intervention due to an AE	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 discontinue study intervention due to an AE for study 1 will be presented.
Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12	Week 12	The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 1 will be presented.
Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
Study 1: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 12	Week 12	The percentage of participants achieving a reduction in CDAI ≥100 points from baseline for study 1 will be presented.
Study 1: Mean Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12	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 to 52-point scale, with lower scores indicating greater fatigue. The mean change from baseline in FACIT-Fatigue score for study 1 will be presented.
Study 1: Percentage of Participants Achieving Endoscopic Remission at Week 12	Week 12	The percentage of participants achieving endoscopic remission, as defined by SES-CD ≤4 and at least 2-point reduction from baseline and no subscore \>1 in any individual variable for study 1 will be presented. SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing), each on a scale from 0 to 3, in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, left colon/sigmoid, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease.
Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Endoscopic Response at Week 12	Week 12	Dx+ participants are those who meet protocol-specific diagnostic assay criteria during screening. The percentage of Dx+ participants achieving endoscopic response, as defined by a ≥50% decrease in simplified endoscopic score for Crohn's disease (CD) from baseline for study 1 and study 2 will be presented.
Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52	Week 52	The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 1 will be presented.
Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 52	Week 52	The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
Study 1: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 52	Week 52	The percentage of participants achieving a reduction in CDAI ≥ 100 points from baseline for study 1 will be presented.
Study 1: Percentage of Participants Achieving Endoscopic Remission at Week 52	Week 52	The percentage of participants achieving endoscopic remission, as defined by SES-CD ≤4 and at least 2-point reduction from baseline and no subscore \>1 in any individual variable for study 1 will be presented. SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing), each on a scale from 0 to 3, in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, left colon/sigmoid, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease.
Study 1: Percentage of Participants Achieving Sustained Clinical Remission per CDAI at Both Week 12 and Week 52	Week 12 and Week 52	The percentage of participants achieving sustained clinical remission, as defined by CDAI score \<150 for study 1 will be presented.
Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per CDAI Score at Week 52	Week 52	The percentage of participants who are in clinical remission as defined by CDAI score \<150 and without corticosteroid use for CD at least 90 days prior to that assessment for study 1 will be presented.
Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52	Week 52	The percentage of participants who are in clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline and without corticosteroid use for CD at least 90 days prior to that assessment for study 1 will be presented.
Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency, Abdominal Pain Score, and Endoscopic Remission at Week 52	Week 52	The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline and achieving endoscopic remission, as defined by SES-CD ≤4 and at least 2-point reduction from baseline and no subscore \>1 in any individual variable for study 1 will be presented.
Study 1: Percentage of Participants Achieving Clinical Remission per CDAI and Endoscopic Remission at Week 52	Week 52	The percentage of participants achieving clinical remission as defined by CDAI score \<150 and achieving endoscopic remission, as defined by SES-CD ≤4 and at least 2-point reduction from baseline and no subscore \>1 in any individual variable for study 1 will be presented.
Study 1: Mean Change from Baseline in FACIT-Fatigue Score at Week 52	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 to 52-point scale, with lower scores indicating greater. The mean change from baseline in FACIT-Fatigue score for study 1 will be presented.
Study 1: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 52	Baseline and Week 52	The IBDQ measures health related quality of life in participants with inflammatory bowel disease. It consists of 32 questions each with a graded response of 1 (worst) to 7 (best). The score ranges between 32 to 224 with higher scores indicating a better quality of life. The mean change from baseline in IBDQ score for study 1 will be presented.
Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12	Week 12	The percentage of participants achieving clinical remission per SF/APS, as defined by average daily SF ≤2.8 and average daily APS ≤1.0 and both not greater than baseline for study 2 will be presented.
Study 2: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 12	Week 12	The percentage of participants achieving a reduction in CDAI ≥ 100 points from baseline for study 2 will be presented.
Study 2: Mean Change from Baseline in FACIT-Fatigue Score at Week 12	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 to 52-point scale, with lower scores indicating greater. The mean change from baseline in FACIT-Fatigue score for study 2 will be presented.
Study 2: Percentage of Participants Achieving Endoscopic Remission at Week 12	Week 12	The percentage of participants achieving endoscopic remission, as defined by SES-CD ≤4 and at least 2-point reduction from baseline and no subscore \>1 in any individual variable for study 2 will be presented. SES-CD evaluates 4 endoscopic variables (ulcer size, ulcerated surface, affected surface, and narrowing), each on a scale from 0 to 3, in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, left colon/sigmoid, and rectum). The total score is the sum of the 4 endoscopic variable scores and ranges from 0 to 56, where higher scores indicate more severe disease.
Study 2: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12	Baseline and Week 12	The IBDQ measures health related quality of life in participants with inflammatory bowel disease. It consists of 32 questions each with a graded response of 1 (worst) to 7 (best). The score ranges between 32 to 224 with higher scores indicating a better quality of life. The mean change from baseline in IBDQ score for study 2 will be presented.
Study 2: Percentage of Participants with Decrease of ≥100 Points in CDAI Score from Baseline to Week 6	Week 6	The percentage of participants achieving a reduction in CDAI ≥ 100 points from baseline for study 2 will be presented.
Study 2: The percentage of Participants with Ulcer-Free Endoscopy at Week 12	Week 12	The percentage of participants achieving ulcer-free endoscopy (mucosal healing), as defined by SES-CD ulcerated surface subscore of 0 in participants with SES-CD ulcerated surface subscore ≥1 at baseline for study 1 will be presented.
Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Clinical Remission per CDAI at Week 12	Week 12	Dx+ participants are those who meet protocol-specific diagnostic assay criteria during screening. The percentage of Dx+ participants achieving clinical remission, as defined by CDAI score \<150 for study 1 and study 2 will be presented.
Study 1: Percentage of Participants with Ulcer-Free Endoscopy at Week 52	Week 52	The percentage of participants achieving ulcer-free endoscopy (mucosal healing), as defined by SES-CD ulcerated surface subscore of 0 in participants with SES-CD ulcerated surface subscore ≥1 at baseline for study 1 will be presented.
Study 2: Percentage of Participants Who Experienced an AE	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 percentage of participants who experience an AE for study 2 will be presented.
Study 2: Percentage of Participants who Discontinue Study Intervention due to an AE	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 percentage of participants who discontinue study intervention due to an AE for study 2 will be presented.
Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score \<150 for study 2 will be presented.

Trial Locations

Locations (446)

Digestive Health Specialists ( Site 5064); 🇺🇸 Dothan, Alabama, United States

Arizona Arthritis & Rheumatology Research, PC ( Site 5094); 🇺🇸 Phoenix, Arizona, United States

GI Alliance - Sun City ( Site 5118); 🇺🇸 Sun City, Arizona, United States

University of Arizona Clinical and Translational Sciences Research Center ( Site 5111); 🇺🇸 Tucson, Arizona, United States

Clinnova Research ( Site 5110); 🇺🇸 Anaheim, California, United States

Southern California Research Center ( Site 5044); 🇺🇸 Coronado, California, United States

Om Research LLC ( Site 5038); 🇺🇸 Lancaster, California, United States

Cedars Sinai Medical Center ( Site 5080); 🇺🇸 Los Angeles, California, United States

UCLA Clinical & Translational Research Center (CTRC) ( Site 5116); 🇺🇸 Los Angeles, California, United States

Om Research LLC ( Site 5045); 🇺🇸 Oxnard, California, United States

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