A Study of Mirikizumab (LY3074828) in Children and Teenagers With Ulcerative Colitis (UC)

Clearance of mirikizumab was evaluated. The PK of mirikizumab is characterized at interim analysis points using mixed-effect (population PK) modelling approaches using the available induction and maintenance mirikizumab concentration data.

Time frame: Predose on week 4, 8, 12,16, 24, 36, 52 and post dose on week 0 and 8

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.

The Abdominal Pain NRS is a single participant-reported item that measures the worst abdominal pain in the past 24 hours using a 6-point scale ranging from 0 (no pain) to 5 (worst possible pain) for 8-11 years old, and 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) for children \< 8 years old as completed by a caregiver and those 12-17 years old. Abdominal Pain NRS Score is calculated by averaging data from all available daily diary entries of abdominal pain NRS for a 7 day period. A negative change from baseline indicates improvement in the participant's Abdominal Pain NRS.

Time frame: Baseline, Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the 7-day average of Abdominal Pain NRS measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

The Abdominal Pain NRS is a single participant-reported item that measures the worst abdominal pain in the past 24 hours using a 6-point scale ranging from 0 (no pain) to 5 (worst possible pain) for 8-11 years old, and 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) for children \< 8 years old as completed by a caregiver and those 12-17 years old. Abdominal Pain NRS Score is calculated by averaging data from all available daily diary entries of abdominal pain NRS for a 7 day period. A negative change from baseline indicates improvement in the participant's Abdominal Pain NRS.

Time frame: Baseline, Week 12

Population: mITT: All randomized participants who received at least one dose of study drug and who had the 7-day average of Abdominal Pain NRS measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Change from Baseline in body weight by gender and age group was calculated.

Time frame: Baseline, Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the body weight measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Observed height velocity by gender and age group was calculated. Age groups for which this was summarized were 2 to \<8, 8 to \<12, and 12 to \<18. Observed height velocity by gender and age group was calculated at baseline according to the following formula: (Present Height \[cm\] - Previous Height \[cm\])/Interval (months) Between Measurements × 12.

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the height velocity measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Clinical remission at week 52 is defined as achieving a 9-point modified Mayo score (MMS) for rectal bleeding (RB) = 0, stool frequency (SF) = 0 or 1 and endoscopy (ES) = 0 or 1 (excluding friability). The MMS is a composite score of ulcerative colitis disease activity calculated as the sum of three subscores: SF subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); RB subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed); ES subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding,ulceration.

Time frame: Week 52

Population: Modified Intention-to-treat population (mITT): All randomized participants who received at least one dose of study drug and who had the clinical remission measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

The PUCAI is a clinician-administered, 6-item questionnaire that measures: abdominal pain; RB; stool consistency; number of stools; nocturnal stools; and activity level. For PUCAI score all items are answered as an average over the 'past 2 days'. A total disease activity score is calculated from 0 to 85, with Severe 65-85; Moderate:35-60; Mild:10-30, and None:\<10. The clinician will record the participant or caregiver/legal guardian responses for the PUCAI electronically as source data in the tablet device at appropriate visits. PUCAI clinical remission is defined as a PUCAI score of \<10 points.

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the clinical remission based on the PUCAI measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Clinical response at week 52 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: SF subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal); RB subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed); ES subscore, based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration)

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the clinical response measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

PUCAI clinical response is defined as a reduction in baseline PUCAI score of ≥20 points.

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the clinical response based on the PUCAI measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Endoscopic remission at week 52 is defined as achieving a Mayo endoscopic subscore of 0 or 1 (excluding friability) at Week 52. ES subscore is based on colonoscopy or sigmoidoscopy and scored from 0 (normal or inactive disease) to 3 (severe disease, spontaneous bleeding, ulceration).

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the endoscopic remission measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Symptomatic remission at week 52 is defined as a Mayo score for RB=0, SF=0 or 1 with ≥ 1 point decrease from baseline. SF subscore, based on the participant's diary and scored from 0 (normal number of stools) to 3 (5 or more stools than normal). RB subscore, based on the participant's diary and scored from 0 (no blood seen) to 3 (blood alone passed).

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the symptomatic remission measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Corticosteroid-free clinical remission was defined as an SF subscore = 0 or 1, RB subscore = 0, ES ≤ 1 (excluding friability), and have not received corticosteroids for ≥ 12 weeks in the 52-Week Treatment Period. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease.

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the modified mayo score clinical remission without the use of corticosteroids measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.

Histologic-endoscopic mucosal remission is defined as achieving both histologic remission and endoscopic remission. Histologic remission is defined as Geboes histological subscores of 0 for parameters: 2B (neutrophils in lamina propria), 3 (neutrophils in epithelium), 4 (crypt destruction), and 5 (erosion or ulceration).

Time frame: Week 52

Population: mITT: All randomized participants who received at least one dose of study drug and who had the histologic-endoscopic mucosal remission measured correctly at baseline. Participants were analysed per their assigned treatment arm regardless of the treatment they actually received.