An Induction Study of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)

Clinical remission at week 12 is defined as achieving a modified Mayo score (MMS) subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline, and endoscopy=0 or 1 (excluding friability), excluding consideration of 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 seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration). The confidence interval of 99.88% was chosen to match the significance level.

Time frame: Week 12

Population: Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

The Urgency NRS is a single participant reported item that measures the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency).Higher scores indicate more severe urgency. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes: treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: \[4-6\] or \[7-9\]), and region (North America/Europe/Other).

Time frame: Baseline, Week 12

Population: mITT population: All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline urgency NRS measurement. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Least square (LS) Mean was calculated using mixed model repeated measures (MMRM) model for post-baseline measures: The MMRM model includes: treatment, baseline value, visit, interaction of baseline value-by-visit, interaction of treatment-by-visit, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: \[4-6\] or \[7-9\]), and region (North America/Europe/Other).

Time frame: Baseline, Week 12

Population: mITT population: All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline fecal calprotectin measurement. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

The IBDQ is a 32-item participant-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. Least square (LS) Mean was calculated using analysis of covariance (ANCOVA) model for post-baseline measures: The ANCOVA model includes: treatment, baseline value, prior biologic or tofacitinib failure (yes/no), baseline corticosteroid use (yes/no), baseline disease activity (MMS: \[4-6\] or \[7-9\]), and region (North America/Europe/Other).

Time frame: Baseline, Week 12

Population: mITT population: All randomized participants who received at least 1 dose of study drug and had a baseline and at least one post-baseline IBDQ measurement. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Clinical response at week 12 is defined as a decrease in the 9-point modified Mayo score (MMS) \[rectal bleeding, stool frequency and the endoscopic findings\] inclusive of \>= 2 points and \>=30% from baseline with either a decrease of rectal bleeding subscore of \>=1 or rectal bleeding subscore of 0 or 1.The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three 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 seen) to 3 (blood alone passed); Endoscopy subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding,ulceration).The MMS ranges from 0 to 9 points,with higher scores representing more severe disease. The confidence interval of 99.88% was chosen to match the significance level.

Time frame: Week 12

Population: mITT Population: All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Endoscopic remission at week 12 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) 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 Mayo endoscopic score ranges from 0 to 3 points, with higher scores representing more severe disease. The confidence interval of 99.88% was chosen to match the significance level.

Time frame: Week 12

Population: mITT Population: All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Endoscopic response at week 12 is defined as achieving at least a 1 point decrease from baseline in the Mayo endoscopic subscore. The Mayo endoscopic subscore ranges from 0 to 3 points, with higher scores representing more severe disease.

Time frame: Week 12

Population: mITT population: All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Histologic remission was assessed using the Geboes histologic scoring system developed for assessment of histologic disease activity in ulcerative colitis. Remission was defined as Geboes histological subscore of 0 for grades: 2b (lamina propria neutrophils), and 3 (neutrophils in epithelium), and 4 (crypt destruction), and 5 (erosion or ulceration).

Time frame: Week 12

Population: mITT population: All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Symptomatic remission at week 12 is defined as a Mayo subscore for rectal bleeding=0, stool frequency=0 or 1 with ≥ 1 point decrease from baseline. 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 seen) to 3 (blood alone passed). The confidence interval of 99.88% was chosen to match the significance level.

Time frame: Week 12

Population: mITT population: All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Symptomatic response at week 12 is defined as ≥30% decrease from baseline in the sum of stool frequency and rectal bleeding 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 seen) to 3 (blood alone passed). The sum of stool frequency and rectal bleeding subscores ranges from 0 to 6.

Time frame: Week 12

Population: mITT population: All randomized participants who received at least one dose of study drug and who had the modified Mayo score measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.

Clearance of mirikizumab was evaluated. Clearance is estimated based on concentration data collected in the time frame of 0-12 weeks.

Time frame: Predose on week 0, week 4, week 8 and post dose on week 0, 4 and 12

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.~As pre-specified in the analysis plan, outcome measures were not reported for ME2 arms,as no formal efficacy analysis was pre-specified for ME2 cohort but only for the main global study arms/groups.