A Phase 2 Safety and Efficacy Study of Tulisokibart (MK-7240/PRA023) in Subjects With Moderately to Severely Active Ulcerative Colitis (MK-7240-005)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.