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

Crohn's Disease Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Program to Evaluate the Efficacy and Safety of Tulisokibart in Participants With Moderately to Severely Active Crohn's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06430801
• Other study ID #: 7240-008
• Secondary ID: MK-7240-0082023-
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 11, 2024
• Est. completion date: September 11, 2029

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this protocol is to evaluate the efficacy and safety of tulisokibart in participants with moderately to severely active Crohn's disease. The primary hypotheses for Study 1 and Study 2 are that tulisokibart is superior to placebo in achieving the coprimary outcome measures of clinical remission by either Crohn's Disease Activity Index (CDAI, primary endpoint recommended by United States Food and Drug Administration [US/FDA]) or stool frequency and abdominal pain score (primary endpoint recommended by European Union European Medicines Agency [EU/EMA]) and endoscopic response.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1200
• Est. completion date: September 11, 2029
• Est. primary completion date: September 11, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 75 Years

Eligibility

The main inclusion and exclusion criteria include but are not limited to the following:

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.

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) within the last 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-anti-TL1A antibody.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

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

Other:
• IV Placebo
Placebo matching IV tulisokibart
• SC Placebo
Placebo matching SC tulisokibart

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Crohn's Disease Activity Index (CDAI) Score at Week 52	The percentage of participants achieving clinical remission, as defined by CDAI score <150 for study 1 will be presented.	Week 52
Primary	Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at 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.	Week 52
Primary	Study 1: Percentage of Participants Achieving Endoscopic Response at 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.	Week 52
Primary	Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score <150 for study 1 will be presented.	Week 12
Primary	Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at 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.	Week 12
Primary	Study 1: Percentage of Participants Achieving Endoscopic Response at 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.	Week 12
Primary	Study 1: Percentage of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience an AE for study 1 will be presented.	Up to approximately 222 weeks
Primary	Study 1: Percentage of Participants who Discontinue Study Intervention due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study intervention due to an AE for study 1 will be presented.	Up to approximately 208 weeks
Primary	Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score <150 for study 2 will be presented.	Week 12
Primary	Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at 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.	Week 12
Primary	Study 2: Percentage of Participants Achieving Endoscopic Response at 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.	Week 12
Primary	Study 2: Percentage of Participants Who Experienced an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience an AE for study 2 will be presented.	Up to approximately 182 weeks
Primary	Study 2: Percentage of Participants who Discontinue Study Intervention due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study intervention due to an AE for study 2 will be presented.	Up to approximately 168 weeks
Secondary	Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at 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.	Week 12
Secondary	Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score <150 for study 1 will be presented.	Week 12
Secondary	Study 1: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 12	The percentage of participants achieving a reduction in CDAI =100 points from baseline for study 1 will be presented.	Week 12
Secondary	Study 1: Mean Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12	The FACIT-Fatigue is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function, scored on a 0 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.	Baseline and Week 12
Secondary	Study 1: Percentage of Participants Achieving Endoscopic Remission at 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, descending 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.	Week 12
Secondary	Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Clinical Remission per CDAI at 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.	Week 12
Secondary	Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Endoscopic Response at 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.	Week 12
Secondary	Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at 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.	Week 52
Secondary	Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 52	The percentage of participants achieving clinical remission, as defined by CDAI score <150 for study 1 will be presented.	Week 52
Secondary	Study 1: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 52	The percentage of participants achieving a reduction in CDAI = 100 points from baseline for study 1 will be presented.	Week 52
Secondary	Study 1: Percentage of Participants Achieving Endoscopic Remission at 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, descending 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.	Week 52
Secondary	Study 1: Percentage of Participants Achieving Sustained Clinical Remission per CDAI at Both 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.	Week 12 and Week 52
Secondary	Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per CDAI Score at 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.	Week 52
Secondary	Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per Stool Frequency and Abdominal Pain Score at 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.	Week 52
Secondary	Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency, Abdominal Pain Score, and Endoscopic Remission at 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.	Week 52
Secondary	Study 1: Percentage of Participants Achieving Clinical Remission per CDAI and Endoscopic Remission at 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.	Week 52
Secondary	Study 1: Mean Change from Baseline in FACIT-Fatigue Score at Week 52	The FACIT-Fatigue is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function, scored on a 0 to 52-point scale, with lower scores indicating greater. The mean change from baseline in FACIT-Fatigue score for study 1 will be presented.	Baseline and Week 52
Secondary	Study 1: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at 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.	Baseline and Week 52
Secondary	Study 1: Percentage of Participants with Ulcer-Free Endoscopy at 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.	Week 52
Secondary	Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at 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.	Week 12
Secondary	Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12	The percentage of participants achieving clinical remission, as defined by CDAI score <150 for study 2 will be presented.	Week 12
Secondary	Study 2: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 12	The percentage of participants achieving a reduction in CDAI = 100 points from baseline for study 2 will be presented.	Week 12
Secondary	Study 2: Mean Change from Baseline in FACIT-Fatigue Score at Week 12	The FACIT-Fatigue is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function, scored on a 0 to 52-point scale, with lower scores indicating greater. The mean change from baseline in FACIT-Fatigue score for study 2 will be presented.	Baseline and Week 12
Secondary	Study 2: Percentage of Participants Achieving Endoscopic Remission at 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, descending 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.	Week 12
Secondary	Study 2: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at 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.	Baseline and Week 12
Secondary	Study 2: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 6	The percentage of participants achieving a reduction in CDAI = 100 points from baseline for study 2 will be presented.	Week 6
Secondary	Study 2: The percentage of Participants with Ulcer-Free Endoscopy at 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.	Week 12

External Links

•   Merck Clinical Trials Information