A Study of Mirikizumab (LY3074828) in Participants With Moderate to Severe Ulcerative Colitis

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.

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.

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.

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.

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).

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).

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).

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."

Pharmacokinetics (PK): Area Under the Concentration-Time Curve During Dosing Interval at Steady State (AUCss, tau) of Mirikizumab

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.

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.

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.

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.