The main purpose of this study is to test the hypothesis that treatment with mirikizumab is superior to placebo in providing clinical benefit to participants with moderate to severe ulcerative colitis (UC). This study will also investigate how the body processes the drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
249
Induction Period: Percentage of Participants With Clinical Remission at Week 12
Clinical remission at week 12 is a defined as achieving a 9-pt Mayo subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1, excluding Physician's Global Assessment (PGA). * Stool Frequency Subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); * Rectal Bleeding Subscore, based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed); * Endoscopy Subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration); * Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from 0 (normal) to 3 (severe disease). The total score ranges from 0 to 9 points, with higher scores representing more severe disease.
Time frame: Week 12
Induction Period: Percentage of Participants With Clinical Response at Week 12
Clinical response at week 12 is defined as a decrease in the 9-point Mayo subscores (rectal bleeding, stool frequency and the endoscopic findings) inclusive of \>= 2 points and \>=35% from baseline with either a decrease of rectal bleeding subscore of \>=1 or rectal bleeding subscore of 0 or 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores: * Stool Frequency Subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); * Rectal Bleeding Subscore, based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed); * Endoscopy Subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The total score ranges from 0 to 9 points, with higher scores representing more severe disease.
Time frame: Week 12
Induction Period: Percentage of Participants With Endoscopic Remission at Week 12
Endoscopic remission at week 12 is defined as achieving a Mayo endoscopic score of 0 at Week 12. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration); The total score ranges from 0 to 3 points, with higher scores representing more severe disease.
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Precision Research Institute, LLC
Chula Vista, California, United States
University of California - San Diego
La Jolla, California, United States
Inland Empire Liver Foundation
Rialto, California, United States
Borland Groover Clinic
Jacksonville, Florida, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Delta Research Partners LLC
Monroe, Louisiana, United States
University of Michigan
Ann Arbor, Michigan, United States
Minnesota Gastroenterology, P.A.
Plymouth, Minnesota, United States
Columbia University Medical Center
New York, New York, United States
Carolinas Healthcare System
Charlotte, North Carolina, United States
...and 66 more locations
Time frame: Week 12
Maintenance Period: Percentage of Participants With Endoscopic Remission at Week 52
Endoscopic remission at week 52 is defined as achieving a Mayo endoscopic subscore of 0 at Week 52. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration); The total score ranges from 0 to 3 points, with higher scores representing more severe disease.
Time frame: Week 52
Induction Period: Change From Baseline to Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score
The IBDQ is a 32-item subject-completed questionnaire that measures 4 aspects of subjects' lives: symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional function, and social function (Guyatt et al. 1989). Responses are graded on a 7-point. Likert scale in which 7 denotes "not a problem at all" and 1 denotes "a very severe problem." Scores range from 32 to 224; a higher score indicates a better quality of life. LS Mean was calculated using MMRM model for post-baseline measures: Variable = Baseline + Geographical Region + Prior Biologic Therapy Group (N) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 12
Induction Period: Change From Baseline to Week 12 in 36-Item Short Form Health Survey (SF-36)
SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Domain scores: general health (range: 5-25); physical functioning (range: 10-30); role-physical (range: 4-8); role-emotional (range: 3-15); social functioning (range: 2-10); bodily pain (range: 2-12); vitality (range: 4-20); mental health (range: 5-25). Each raw scale score was converted to a scale score ranging from 0-100 points, with higher values representing a better outcome \[(Raw score) - min{raw score}\] / (max {raw score} - min{raw score}) x 100\]. LS Mean was calculated using Mixed effect Model Repeat Measurement (MMRM) model for post-baseline measures: Variable = Baseline + Geographical Region + Prior Biologic Therapy Group (N) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 12
Induction Period: Change From Baseline to Week 12 in Patient's Global Impressions of Severity (PGI-S) Score
PGI-S is a 1-item subject-rated questionnaire designed to assess the subject's impression of their disease symptoms at baseline (Guy 1976; Yalcin and Bump 2003). Responses are graded on a 7-point scale in which a score of 1 indicates that the subject's symptom(s) are "normal," a score of 2 indicates that the subject feels "borderline ill," a score of 3 indicates that the subject feels "mildly ill," a score of 4 indicates that the subject(s) feel "moderately ill," and scores of 5, 6, and 7 indicate that the subject feels "markedly ill," "severely ill," and "extremely ill," respectively. LS Mean was calculated using MMRM model for post-baseline measures: Variable = Baseline + Geographical Region + Prior Biologic Therapy Group (N) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 12
Induction Period: Patient's Global Impressions of Improvement (PGI-I) Score at Week 12
PGI-I scale is a subject-rated instrument designed to assess the subject's impression of change in their symptom(s) (Guy 1976; Yalcin and Bump 2003). Responses are graded on a 7-point Likert scale in which a score of 1 indicates that the subject's symptom(s) is "very much better," a score of 4 indicates that the subject's symptom(s) has experienced "no change," and a score of 7 indicates that the subject's symptom(s) is "very much worse."
Time frame: Week 12
Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, Tau) of Mirikizumab
Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, tau) of Mirikizumab
Time frame: Induction Period: Day (D) 1, D15 ± 2d, D29 ± 2d, D43 ± 2d, D57 ± 2d, D78-85; Maintenance Period: D85-92,D113± 7d,D141± 7d,D169± 7d,D225 ±7d,D281 ±7d,D337 ±7d,D393± 7d,D448± 7d,D504± 7d,D560± 7d,D616± 7d,D672± 7d,D728± 7d,D784± 7d,D840± 7d
Induction Period: Percentage of Participants With Symptomatic Remission at Week 12
Symptomatic remission is defined as a stool frequency score of 0 or 1 and a rectal bleeding score of 0. * Stool Frequency Subscore is based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal). * Rectal Bleeding Subscore is based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed). The total score ranges from 0 to 1 points, with higher scores representing more severe disease. The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Time frame: Week 12
Maintenance Period: Percentage of Participants With Symptomatic Remission at Week 52
Symptomatic remission is defined as a stool frequency score of 0 or 1 and a rectal bleeding score of 0. * Stool Frequency Subscore , based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); * Rectal Bleeding Subscore , based on the participant's diary and scored from 0 (no blood) to 3 (blood only passed); * Endoscopy Subscore , based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration); * Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from zero (normal) to 3 (severe disease). The total score ranges from 0 to 1 points, with higher scores representing more severe disease. The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Time frame: Week 52
Induction Period: Percentage of Participants With Endoscopic Improvement at Week 12
Endoscopic Improvement defined as achieving an endoscopic findings subscore of 0 or 1. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Time frame: Week 12
Maintenance Period: Percentage of Participants With Endoscopic Improvement at Week 52
Endoscopic Improvement defined as achieving an endoscopic findings subscore of 0 or 1. Endoscopy Subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The percentage of response is calculated by dividing number of participants in the specified category by number of participants with non-missing values multiplied by 100.
Time frame: Week 52