Crohn's Disease
Conditions
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.
Interventions
DRUGIV Tulisokibart
Humanized monoclonal antibody that binds human tumor necrosis factor-like cytokine 1A (TL1A), administered intravenously
DRUGSC Tulisokibart
Humanized monoclonal antibody that binds human TL1A, administered subcutaneously
OTHERIV Placebo
Placebo matching IV tulisokibart
OTHERSC Placebo
Placebo matching SC tulisokibart
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 [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 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. |
| Study 1 [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 1 will be presented. |
| Study 1 [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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study 1: Number 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 number of participants who experience an AE for Study 1 will be presented. |
| Study 1: Number 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 number 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 Clinical Response per CDAI Score (Decrease From Baseline of ≥100 Points) at Week 12 | 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. |
| 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 Clinical Remission per CDAI Score 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 and 2: Percentage of Participants in 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: Percentage of Participants With Clinical Response (Decrease From Baseline at Least 100 Points) or Clinical Remission (<150) per CDAI Score at Week 6 | 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. |
| 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 [EU/EMA Only]: 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 Clinical Response per CDAI Score (Decreased From Baseline of ≥100 Points) at Week 52 | 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. |
| 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 [US/FDA Only]: 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 [EU/EMA Only]: 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 Score 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 [EU/EMA Only]: 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 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: Number 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 number of participants who experience an AE for Study 2 will be presented. |
| Study 2: Number 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 number of participants who discontinue study intervention due to an AE for Study 2 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 [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. |
| Study 2: Percentage of Participants With Clinical Response per CDAI Score (Decreased From Baseline of ≥100 Points) at Week 12 | 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. |
| 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 [EU/EMA Only]: Mean Change From Baseline in 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 Clinical Response (Decreased From Baseline of ≥100 Points) or Clinical Remission (<150) per CDAI Score at Week 6 | 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. |
| Study 2: 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 2 will be presented. |
Countries
Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Dominican Republic, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Peru, Poland, Portugal, Romania, Saudi Arabia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed