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 3RecruitingNCT06430801

Merck Sharp & Dohme LLC1,200 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,200

Conditions

Crohn's Disease

Interventions

IV TulisokibartDRUG

Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously

SC TulisokibartDRUG

Humanized monoclonal antibody that binds human TL1A, administered subcutaneously

IV PlaceboOTHER

Placebo matching IV tulisokibart

SC PlaceboOTHER

Placebo matching SC tulisokibart

Eligibility

Sex: ALLMin age: 16 YearsMax age: 80 Years

Medical Language ↔ Plain English

The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * Has had a diagnosis of Crohn's disease (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 CD. * 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-tumor necrosis factor-like cytokine 1A (TL1A) antibody (Ab).

Locations (499)

Digestive Health Specialists ( Site 5064)

Dothan, Alabama, United States

COMPLETED

Arizona Arthritis & Rheumatology Research, PC ( Site 5094)

Phoenix, Arizona, United States

COMPLETED

GI Alliance - Sun City ( Site 5118)

Sun City, Arizona, United States

RECRUITING

University of Arizona Clinical and Translational Sciences Research Center ( Site 5111)

Tucson, Arizona, United States

Outcomes

Primary Outcomes

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.

Time frame: Week 52

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.

Time frame: Week 52

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.

Time frame: Week 52

Study 1 [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 1 will be presented.

Time frame: Week 12

Study 1 [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 1 will be presented.

Time frame: Week 12

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.

Time frame: Week 12

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.

Time frame: Week 12

Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12

Time frame: Week 12

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.

Time frame: Week 12

Secondary Outcomes

Study 1: Number 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 number of participants who experience an AE for Study 1 will be presented.

Time frame: Up to approximately 52 weeks

Study 1: Number of Participants Who Discontinue Study Intervention due to an AE

Time frame: Up to approximately 52 weeks

Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12

Time frame: Week 12

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.

Time frame: Week 12

Study 1: Percentage of Participants With Clinical Response per CDAI Score (Decrease From Baseline of ≥100 Points) at Week 12

The percentage of participants achieving clinical response, defined as decrease from baseline of ≥100 points in CDAI for Study 1 will be presented.

Central Contacts

Toll Free Number

CONTACT

1-888-577-8839 Trialsites@msd.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of Arkansas for Medical Sciences ( Site 5147)

Little Rock, Arkansas, United States

RECRUITING

Clinnova Research ( Site 5110)

Anaheim, California, United States

RECRUITING

Southern California Research Center ( Site 5044)

Coronado, California, United States

RECRUITING

Om Research LLC ( Site 5038)

Lancaster, California, United States

RECRUITING

Cedars Sinai Medical Center ( Site 5080)

Los Angeles, California, United States

RECRUITING

UCLA Clinical & Translational Research Center (CTRC) ( Site 5116)

Los Angeles, California, United States

RECRUITING

...and 489 more locations

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.

Time frame: Baseline and Week 12

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, 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.

Time frame: Week 12

Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Clinical Remission per CDAI Score 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.

Time frame: Week 12

Study 1 and 2: Percentage of Participants in 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.

Time frame: Week 12

Study 1: Percentage of Participants With Clinical Response (Decrease From Baseline at Least 100 Points) or Clinical Remission (<150) per CDAI Score at Week 6

The percentage of participants achieving clinical response (defined as decrease from baseline of ≥100 points in CDAI) or clinical remission (defined as CDAI \<150) for Study 1 will be presented.

Time frame: Week 6

Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52

Time frame: Week 52

Study 1 [EU/EMA Only]: 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.

Time frame: Week 52

Study 1: Percentage of Participants With Clinical Response per CDAI Score (Decreased From Baseline of ≥100 Points) at Week 52

The percentage of participants achieving clinical response, defined as decrease from baseline of ≥100 points in CDAI for Study 1 will be presented.

Time frame: Week 52

Study 1: Percentage of Participants Achieving Endoscopic Remission at Week 52

Time frame: Week 52

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.

Time frame: Week 12 and Week 52

Study 1 [US/FDA Only]: 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.

Time frame: Week 52

Study 1 [EU/EMA Only]: 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.

Time frame: Week 52

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.

Time frame: Week 52

Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score 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.

Time frame: Week 52

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.

Time frame: Baseline and Week 52

Study 1 [EU/EMA Only]: 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.

Time frame: Baseline and Week 52

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.

Time frame: Week 52

Study 2: Number of Participants Who Experienced an AE

Time frame: Up to approximately 12 weeks

Study 2: Number of Participants Who Discontinue Study Intervention due to an AE

Time frame: Up to approximately 12 weeks

Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12

Time frame: Week 12

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.

Time frame: Week 12

Study 2: Percentage of Participants With Clinical Response per CDAI Score (Decreased From Baseline of ≥100 Points) at Week 12

The percentage of participants achieving clinical response, defined as decrease from baseline of ≥100 points in CDAI for Study 2 will be presented.

Time frame: Week 12

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.

Time frame: Baseline and Week 12

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, 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.

Time frame: Week 12

Study 2 [EU/EMA Only]: Mean Change From Baseline in IBDQ Score at Week 12

Time frame: Baseline and Week 12

Study 2: Percentage of Participants With Clinical Response (Decreased From Baseline of ≥100 Points) or Clinical Remission (<150) per CDAI Score at Week 6

The percentage of participants achieving clinical response (defined as decrease from baseline of ≥100 points in CDAI) or clinical remission (defined as CDAI \<150) for Study 2 will be presented.

Time frame: Week 6

Study 2: Percentage of Participants With Ulcer-Free Endoscopy at Week 12

Time frame: Week 12