Ulcerative Colitis
Conditions
Keywords
ARTEMIS-UC, ARTEMIS, Ulcerative Colitis
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.
Interventions
DRUGTulisokibart
Administered by IV infusion
DEVICECompanion Diagnostic (CDx) Testing
PRA023 CDx Genotyping Assay
OTHERPlacebo
Placebo administered by IV infusion
Sponsors
Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 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 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 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 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 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 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Georgia, Hungary, Israel, Italy, Poland, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Participants with moderately to severely active ulcerative colitis were enrolled.
Pre-assignment details
Participants responding to treatment at Induction Period Week 12 could enter the Open-label Extension (OLE). Week 12 nonresponders could receive open-label induction treatment and, if they responded at Week 26, could entered the OLE. Week 12 and Week 26 responders were rerandomized in the OLE to receive either 100 mg or 250 mg tulisokibart. Participants on 100 mg tulisokibart could escalate to 250 mg if disease activity was uncontrolled.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Tulisokibart Participants who were CDx+ and CDx- received 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. | 68 |
| Cohort 1 Placebo Participants who were CDx+ and CDx- received 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. | 67 |
| Cohort 2 Tulisokibart Participants who were CDx+ received 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. | 22 |
| Cohort 2 Placebo Participants who were CDx+ received 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. | 21 |
| Total | 178 |
Baseline characteristics
| Characteristic | Cohort 1 Placebo | Cohort 1 Tulisokibart | Total | Cohort 2 Placebo | Cohort 2 Tulisokibart |
|---|---|---|---|---|---|
| Age, Continuous | 42.2 Years STANDARD_DEVIATION 16.3 | 40.4 Years STANDARD_DEVIATION 14.4 | 40.6 Years STANDARD_DEVIATION 15.3 | 38.5 Years STANDARD_DEVIATION 11.4 | 38.1 Years STANDARD_DEVIATION 18.2 |
| Baseline 3-Component Modified Mayo Score | 7.1 Score STANDARD_DEVIATION 1.1 | 6.9 Score STANDARD_DEVIATION 1.21 | 7.0 Score STANDARD_DEVIATION 1.16 | 6.7 Score STANDARD_DEVIATION 1.27 | 7.1 Score STANDARD_DEVIATION 1.01 |
| Baseline Endoscopic Score Score of 2 | 14 Participants | 22 Participants | 48 Participants | 9 Participants | 3 Participants |
| Baseline Endoscopic Score Score of 3 | 53 Participants | 46 Participants | 130 Participants | 12 Participants | 19 Participants |
| Baseline High sensitivity C-reactive protein (hsCRP) | 10.022 mg/L STANDARD_DEVIATION 13.7709 | 10.162 mg/L STANDARD_DEVIATION 19.191 | 10.182 mg/L STANDARD_DEVIATION 16.243 | 10.155 mg/L STANDARD_DEVIATION 16.6271 | 10.754 mg/L STANDARD_DEVIATION 13.9272 |
| Baseline Total Modified Mayo Score | 9.4 Score STANDARD_DEVIATION 1.29 | 9.1 Score STANDARD_DEVIATION 1.49 | 9.2 Score STANDARD_DEVIATION 1.39 | 8.9 Score STANDARD_DEVIATION 1.59 | 9.3 Score STANDARD_DEVIATION 1.1 |
| Body Mass Index (BMI) | 25.52 Weight (kg) / [Height (m)]^2 STANDARD_DEVIATION 5.033 | 25.71 Weight (kg) / [Height (m)]^2 STANDARD_DEVIATION 7.029 | 25.63 Weight (kg) / [Height (m)]^2 STANDARD_DEVIATION 5.845 | 26.37 Weight (kg) / [Height (m)]^2 STANDARD_DEVIATION 5.518 | 25.11 Weight (kg) / [Height (m)]^2 STANDARD_DEVIATION 4.539 |
| CDx+/CDx- CDx- | 51 Participants | 52 Participants | 103 Participants | 0 Participants | 0 Participants |
| CDx+/CDx- CDx+ | 16 Participants | 16 Participants | 75 Participants | 21 Participants | 22 Participants |
| Concomitant UC Medication Use Aminosalicylate | 45 Participants | 44 Participants | 119 Participants | 14 Participants | 16 Participants |
| Concomitant UC Medication Use Immunomodulator | 11 Participants | 8 Participants | 21 Participants | 0 Participants | 2 Participants |
| Concomitant UC Medication Use Oral Corticosteroid | 38 Participants | 35 Participants | 88 Participants | 7 Participants | 8 Participants |
| Current smoking status Current | 3 Participants | 9 Participants | 15 Participants | 0 Participants | 3 Participants |
| Current smoking status Former | 19 Participants | 20 Participants | 55 Participants | 10 Participants | 6 Participants |
| Current smoking status Never | 45 Participants | 39 Participants | 108 Participants | 11 Participants | 13 Participants |
| Duration of Ulcerative Colitis (UC) | 6.277 Years STANDARD_DEVIATION 6.1942 | 6.680 Years STANDARD_DEVIATION 6.3766 | 6.866 Years STANDARD_DEVIATION 6.2239 | 10.351 Years STANDARD_DEVIATION 6.8957 | 5.911 Years STANDARD_DEVIATION 4.0708 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 8 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants | 60 Participants | 160 Participants | 19 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 10 Participants | 1 Participants | 2 Participants |
| Extent of UC Left sided colitis | 28 Participants | 35 Participants | 81 Participants | 8 Participants | 10 Participants |
| Extent of UC Pancolitis | 32 Participants | 31 Participants | 85 Participants | 12 Participants | 10 Participants |
| Extent of UC Proctosigmoiditis | 7 Participants | 2 Participants | 12 Participants | 1 Participants | 2 Participants |
| Height | 172.61 Centimeters (cm) STANDARD_DEVIATION 9.185 | 169.91 Centimeters (cm) STANDARD_DEVIATION 9.798 | 171.61 Centimeters (cm) STANDARD_DEVIATION 9.317 | 173.26 Centimeters (cm) STANDARD_DEVIATION 8.418 | 172.31 Centimeters (cm) STANDARD_DEVIATION 8.729 |
| Prior Treatment for UC Biologic/Biologic-Like Use (Prior Medications) No | 35 Participants | 36 Participants | 91 Participants | 11 Participants | 9 Participants |
| Prior Treatment for UC Biologic/Biologic-Like Use (Prior Medications) Yes | 32 Participants | 32 Participants | 87 Participants | 10 Participants | 13 Participants |
| Prior Treatment for UC Biologic/Biologic-Like Use (stratification) No | 32 Participants | 33 Participants | 84 Participants | 9 Participants | 10 Participants |
| Prior Treatment for UC Biologic/Biologic-Like Use (stratification) Yes | 35 Participants | 35 Participants | 94 Participants | 12 Participants | 12 Participants |
| Prior Treatment for UC Corticosteroid | 58 Participants | 51 Participants | 142 Participants | 16 Participants | 17 Participants |
| Prior Treatment for UC Immunomodulators | 28 Participants | 22 Participants | 62 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 12 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 57 Participants | 65 Participants | 159 Participants | 20 Participants | 17 Participants |
| Sex: Female, Male Female | 29 Participants | 34 Participants | 77 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 38 Participants | 34 Participants | 101 Participants | 17 Participants | 12 Participants |
| Time Since Symptom Onset | 6.661 Years STANDARD_DEVIATION 5.7342 | 7.422 Years STANDARD_DEVIATION 6.2596 | 7.449 Years STANDARD_DEVIATION 6.0077 | 11.367 Years STANDARD_DEVIATION 6.5819 | 6.221 Years STANDARD_DEVIATION 4.0697 |
| Weight | 76.59 Kilograms (kg) STANDARD_DEVIATION 18.482 | 73.89 Kilograms (kg) STANDARD_DEVIATION 19.653 | 75.64 Kilograms (kg) STANDARD_DEVIATION 18.135 | 79.36 Kilograms (kg) STANDARD_DEVIATION 14.984 | 74.62 Kilograms (kg) STANDARD_DEVIATION 14.985 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 67 | 0 / 22 | 0 / 21 | 0 / 82 | 0 / 41 | 0 / 46 | 0 / 31 | 0 / 27 | 0 / 24 | 0 / 13 |
| other Total, other adverse events | 14 / 68 | 10 / 67 | 2 / 22 | 6 / 21 | 12 / 82 | 23 / 41 | 28 / 46 | 16 / 31 | 15 / 27 | 11 / 24 | 10 / 13 |
| serious Total, serious adverse events | 0 / 68 | 6 / 67 | 1 / 22 | 1 / 21 | 0 / 82 | 3 / 41 | 2 / 46 | 0 / 31 | 3 / 27 | 1 / 24 | 0 / 13 |
Outcome results
Primary
Percentage of Participants in Cohort 1 Achieving Clinical Remission
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 Achieving Clinical Remission | 26.5 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 Achieving Clinical Remission | 1.5 Percentage of participants |
p-value: <0.000195% CI: [11.8, 36.5]Cochran-Mantel-Haenszel
Primary
Percentage of Participants Who Discontinued Due to an AE
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.
Time frame: Up to ~14 weeks
Population: All randomized participants who received at least one dose of study intervention regardless of assigned cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Discontinued Due to an AE | 1.1 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Discontinued Due to an AE | 3.4 Percentage of participants |
Primary
Percentage of Participants Who Experienced an Adverse Event (AE)
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.
Time frame: Up to ~14 weeks
Population: All randomized participants who received at least one dose of study intervention regardless of assigned cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Experienced an Adverse Event (AE) | 45.6 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Experienced an Adverse Event (AE) | 43.2 Percentage of participants |
Primary
Percentage of Participants Who Had One or More Serious Adverse Events
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.
Time frame: Up to ~14 weeks
Population: All randomized participants who received at least one dose of study intervention regardless of assigned cohort
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Had One or More Serious Adverse Events | 1.1 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Had One or More Serious Adverse Events | 8.0 Percentage of participants |
Secondary
Percentage of Participants in Cohort 1 Achieving Clinical Response
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 Achieving Clinical Response | 66.2 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 Achieving Clinical Response | 22.4 Percentage of participants |
p-value: <0.000195% CI: [27.4, 56.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Cohort 1 With an Inflammatory Bowel Disease Questionnaire (IBDQ) Response
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 With an Inflammatory Bowel Disease Questionnaire (IBDQ) Response | 82.4 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 With an Inflammatory Bowel Disease Questionnaire (IBDQ) Response | 49.3 Percentage of participants |
p-value: <0.000195% CI: [17.2, 46.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Cohort 1 With Endoscopic Improvement
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 With Endoscopic Improvement | 36.8 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 With Endoscopic Improvement | 6.0 Percentage of participants |
p-value: <0.000195% CI: [17.4, 43.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Healing
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention and had baseline and Week 12 data for Geboes Scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Healing | 30.8 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Healing | 3.5 Percentage of participants |
p-value: <0.000195% CI: [14.3, 39.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Improvement
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention and had baseline and Week 12 Geboes scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Improvement | 30.8 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 With Histologic-endoscopic Mucosal Improvement | 3.5 Percentage of participants |
p-value: <0.000195% CI: [14.3, 39.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Cohort 1 With Histologic Improvement
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention and had baseline and Week 12 Geboes scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 With Histologic Improvement | 46.2 Percentage |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 With Histologic Improvement | 17.5 Percentage |
p-value: 0.000995% CI: [12.1, 42.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants in Cohort 1 With Symptomatic Remission
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.
Time frame: Baseline and Week 12
Population: All randomized participants in Cohort 1 who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants in Cohort 1 With Symptomatic Remission | 19.1 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants in Cohort 1 With Symptomatic Remission | 6.0 Percentage of participants |
p-value: 0.022395% CI: [1.8, 24.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Are CDx+ (Cohorts 1 + 2) Who Had an IBDQ Response
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.
Time frame: Baseline and Week 12
Population: All randomized participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Are CDx+ (Cohorts 1 + 2) Who Had an IBDQ Response | 76.3 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Are CDx+ (Cohorts 1 + 2) Who Had an IBDQ Response | 56.8 Percentage of participants |
95% CI: [-1.7, 38.7]
Secondary
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Remission
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.
Time frame: Baseline and Week 12
Population: All randomized participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Remission | 31.6 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Remission | 10.8 Percentage of participants |
p-value: 0.022495% CI: [2.1, 37.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Response
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.
Time frame: Baseline and Week 12
Population: All randomized participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Response | 55.3 Percentage of Participants |
| Cohort 1 Placebo | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Clinical Response | 32.4 Percentage of Participants |
95% CI: [0.4, 42.2]
Secondary
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Endoscopic Improvement
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.
Time frame: Baseline and Week 12
Population: All randomized participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Endoscopic Improvement | 36.8 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Endoscopic Improvement | 18.9 Percentage of participants |
95% CI: [-2.4, 36.4]
Secondary
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Healing
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.
Time frame: Baseline and Week 12
Population: All randomized participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention and had baseline and Week 12 data for Geboes Scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Healing | 38.9 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Healing | 16.7 Percentage of participants |
95% CI: [0.2, 41]
Secondary
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Improvement
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.
Time frame: Baseline and Week 12
Population: All participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention and had baseline and Week 12 data for Geboes Scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Improvement | 38.9 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic-endoscopic Mucosal Improvement | 16.7 Percentage of participants |
95% CI: [0.2, 41]
Secondary
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic Improvement
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.
Time frame: Baseline and Week 12
Population: All randomized participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention and had baseline and Week 12 data for Geboes Scores
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic Improvement | 55.6 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Histologic Improvement | 26.7 Percentage of participants |
95% CI: [5, 48.3]
Secondary
Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Symptomatic Remission
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.
Time frame: Baseline and Week 12
Population: All randomized participants who were CDx+ (Cohorts 1 + 2), who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 Tulisokibart | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Symptomatic Remission | 21.1 Percentage of participants |
| Cohort 1 Placebo | Percentage of Participants Who Were CDx+ (Cohorts 1 + 2) With Symptomatic Remission | 10.8 Percentage of participants |
95% CI: [-6.9, 26.9]