A Phase 2 Safety and Efficacy Study of Tulisokibart (MK-7240/PRA023) in Subjects With Moderately to Severely Active Ulcerative Colitis (MK-7240-005)
- Conditions
- Ulcerative Colitis
- Interventions
- Registration Number
- NCT04996797
- Lead Sponsor
- Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Brief Summary
The purpose of this study is to assess the safety and efficacy of tulisokibart in participants with moderately to severely active Ulcerative Colitis (UC). After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 178
The main inclusion criteria include but are not limited to the following:
- Confirmed diagnosis of ulcerative colitis (UC)
- Has moderately to severely active UC as defined by 3-component Modified Mayo score
- Must have corticosteroid dependence or have had no response, insufficient response, loss of response, and/or intolerance to at least one of the following therapies: corticosteroid, immunosuppressants, or an approved anti-tumor necrosis factor (anti-TNF), anti-integrin, anti-interleukin 12/23 (anti-IL12/23), Janus kinase (JAK) inhibitor, Sphingosine 1-phosphate receptor (S1PR) modulator.
The main exclusion criteria include but are not limited to the following:
- Has diagnosis of Crohn's disease or indeterminate colitis
- Has current evidence of fulminant colitis, toxic megacolon, bowel perforation, total proctocoloectomy or partial colectomy
- Has current or impending need for colostomy or ileostomy
- Has had surgical bowel resection within 3 months before screening
- Has past or current evidence of definite low-grade or high-grade colonic dysplasia not completely removed
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 Tulisokibart Tulisokibart Participants who are CDx+ will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0 and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. Cohort 1 Tulisokibart Tulisokibart Participants who are CDx+ and CDx- will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0, and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. Cohort 2 Placebo Companion Diagnostic (CDx) Testing Participants who are CDx+ will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. Cohort 1 Placebo Placebo Participants who are CDx+ and CDx- will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. Cohort 2 Tulisokibart Companion Diagnostic (CDx) Testing Participants who are CDx+ will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0 and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. Cohort 2 Placebo Placebo Participants who are CDx+ will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Discontinued Due to an AE Up to ~14 weeks An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants who discontinued due to an AE is reported.
Percentage of Participants in Cohort 1 Achieving Clinical Remission Baseline and Week 12 The 3-component Modified Mayo Score (MMS) ranges from 0 to 9 and is composed of endoscopic assessment, rectal bleeding (RB), and stool frequency (SF) subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Clinical remission is defined as endoscopic subscore of 0 or 1, RB subscore of 0, and SF subscore of 0 or 1 and not greater than baseline. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants Who Had One or More Serious Adverse Events Up to ~14 weeks Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Serious adverse events are defined as: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL), Life-threatening consequences; urgent intervention indicated, and death. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants experiencing a serious AE are presented.
Percentage of Participants Who Experienced an Adverse Event (AE) Up to ~14 weeks An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Reported adverse experiences used the Common Terminology for Adverse Events (CTCAE) Version 4.0. Per protocol, adverse events are reported by treatment with tulisokibart or placebo regardless of assigned cohort. Participants received identical treatment regiments regardless of cohort. The percentage of participants who experienced at least one AE is reported.
- Secondary Outcome Measures
Name Time Method Percentage of Participants in Cohort 1 With Symptomatic Remission Baseline and Week 12 RB, and SF subscores each range from 0 to 3, with higher scores indicating more severe disease. Symptomatic remission is defined as participants with SF subscore = 0 and RB subscore = 0. The percentage of participants who achieved symptomatic remission is presented. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Improvement Baseline and Week 12 Histologic-endoscopic mucosal improvement is defined as a Geboes score ≤ 3.1 and endoscopy subscore of the MMS ≤ 1 with no friability. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. The endoscopic subscore of the MMS ranges from 0-3. For both scales a higher score indicates more severe disease. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Response Baseline and Week 12 The 3-component MMS ranges from 0 to 9 and is composed of endoscopic assessment, RB, and SF subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Clinical response is defined by reduction from Baseline ≥ 2 points and ≥ 30% in 3-component Modified Mayo Score, accompanied by a reduction ≥ 1 in RB subscore or absolute RB subscore ≤ 1. Per protocol participants who were CDx+ (Cohort 1 + Cohort 2) were analyzed for this outcome measure.
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Symptomatic Remission Baseline and Week 12 RB, and SF subscores each range from 0 to 3, with higher scores indicating more severe disease. Symptomatic remission is defined as participants with SF subscore = 0 and RB subscore = 0. The percentage of participants who achieved symptomatic remission is presented. Per protocol participants who were CDx+ (Cohort 1 + Cohort 2) were analyzed for this outcome measure.
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic Improvement Baseline and Week 12 Histologic improvement is defined as Geboes score ≤ 3.1. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. A higher score indicates more severe disease. Per protocol participants who were CDx+ (Cohorts 1 + 2) were analyzed for this outcome measure.
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Endoscopic Improvement Baseline and Week 12 The 3-component MMS ranges from 0 to 9 and is composed of endoscopic assessment, RB, and SF subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Endoscopic improvement is defined by endoscopy subscore of MMS of ≤ 1 with no friability. Per protocol participants who were CDx+ (Cohort 1 + Cohort 2) were analyzed for this outcome measure.
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Improvement Baseline and Week 12 Histologic-endoscopic mucosal improvement is defined as a Geboes score ≤ 3.1 and endoscopy subscore of the MMS ≤ 1 with no friability. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. The endoscopic subscore of the MMS ranges from 0-3. For both scales a higher score indicates more severe disease. Per protocol participants who were CDx+ (Cohorts 1 + 2) were analyzed for this outcome measure.
Percentage of Participants in Cohort 1 With Endoscopic Improvement Baseline and Week 12 The 3-component MMS ranges from 0 to 9 and is composed of endoscopic assessment, RB, and SF subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Endoscopic improvement is defined by endoscopy subscore of the MMS of ≤ 1 with no friability. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants in Cohort 1 Achieving Clinical Response Baseline and Week 12 The 3-component MMS ranges from 0 to 9 and is composed of endoscopic assessment, RB, and SF subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Clinical response is defined as a reduction from Baseline ≥ 2 points and ≥ 30% in 3-component Modified Mayo Score, accompanied by a reduction ≥ 1 in RB subscore or absolute RB subscore ≤ 1. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Remission Baseline and Week 12 The 3-component MMS ranges from 0 to 9 and is composed of endoscopic assessment, RB, and SF subscores with each of the components ranging from 0 to 3, with higher scores indicating more severe disease. Clinical remission is defined as endoscopic subscore of 0 or 1, RB subscore of 0, and SF subscore of 0 or 1 and not greater than baseline. Per protocol participants who were CDx+ (Cohort 1 + Cohort 2) were analyzed for this outcome measure.
Percentage of Participants in Cohort 1 With Histologic Improvement Baseline and Week 12 Histologic improvement is defined as Geboes score ≤ 3.1. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. A higher score indicates more severe disease. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Healing Baseline and Week 12 Histologic-endoscopic mucosal improvement is defined as Geboes score ≤ 2B.1 and endoscopy subscore of MMS ≤ 1 with no friability. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. The endoscopic subscore of the MMS ranges from 0-3. For both scales a higher score indicates more severe disease. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants in Cohort 1 With an Inflammatory Bowel Disease Questionnaire (IBDQ) Response Baseline and Week 12 IBDQ is a self-administered, disease-specific Health-Related Quality of Life (HRQOL) instrument for subjects with IBD. The IBDQ covers 4 dimensions and 32 questions: bowel symptoms, systemic symptoms, emotional function, and social function. Items are scored on a 7-point Likert scale (1 = all of the time and 7 = none of the time), for a total global score in the range 32 to 224 (with higher scores indicating better HRQOL). IBDQ response, as defined by ≥ 16-point increase from Baseline at Week 12. Per protocol participants in Cohort 1 were analyzed for this outcome measure.
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Healing Baseline and Week 12 Histologic-endoscopic mucosal improvement is defined as Geboes score ≤ 2B.1 and endoscopy subscore of MMS ≤ 1 with no friability. The Geboes histologic index includes 7 histological features (architectural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulcers). The Geboes score has 6 grades from 0 to 5, with each grade of the score divided into 4 or 5 subcategories; the score ranges from 0.0 to 5.4. The endoscopic subscore of the MMS ranges from 0-3. For both scales a higher score indicates more severe disease. Per protocol participants who were CDx+ (Cohorts 1 + 2) were analyzed for this outcome measure.
Percentage of Participants Who Are CDx+ (Cohorts 1 + 2) Who Had an IBDQ Response Baseline and Week 12 IBDQ is a self-administered, disease-specific Health-Related Quality of Life (HRQOL) instrument for subjects with IBD. The IBDQ covers 4 dimensions and 32 questions: bowel symptoms, systemic symptoms, emotional function, and social function. Items are scored on a 7-point Likert scale (1 = all of the time and 7 = none of the time), for a total global score in the range 32 to 224 (with higher scores indicating better HRQOL). IBDQ response, as defined by ≥ 16-point increase from Baseline at Week 12. Per protocol participants who were CDx+ (Cohorts 1 + 2) were analyzed for this outcome measure.
Trial Locations
- Locations (4)
Prometheus Biosciences Selected Center
🇭🇺Budapest, Hungary
Prometheus Biosciences Selected Site #2
🇵🇱Warsaw, Poland
Prometheus Biosciences Selected Site
🇬🇧Prescot, Merseyside, United Kingdom
Prometheus Biosciences Selected Sites
🇬🇧London, United Kingdom