A Study of Mirikizumab (LY3074828) in Participants With Crohn's Disease

Clinical response by PRO defined as ≥ 30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Clinical remission defined as Crohn's Disease Activity Index (CDAI) total score \<150. The CDAI is an 8-item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter \[hematocrit\]).. Total score range of 0 to 600 points.

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Clinical response by patient reported outcome (PRO) defined as ≥30% decrease in stool frequency (SF) and/or abdominal pain (AP) & neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Endoscopic response defined as ≥50% reduction from baseline in total Simple Endoscopic Score for Crohn's Disease (SES-CD) score. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none=0; diameter 0.1-0.5 cm=1; 0.5-2 cm=2; \>2 cm=3); extent of ulcerated surface (none=0; \<10%=1; 10% to 30%=2; \>30%=3); extent of affected surface (none=0; \<50%=1; 50% to 75%=2; \>75%=3); presence & type of narrowing (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease.

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

PopPK: AUC of Mirikizumab

Time frame: 900 mg Mirikizumab: Week 4: Predose; Week 4, Day 1: Postdose; Week 8, 12: Predose 300 mg Mirikizumab: Week 16, 24, 36: Predose; Week 52

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

Change from baseline in CRP

Time frame: Baseline, Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Change from baseline in Fecal Calprotectin

Time frame: Baseline, Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug and had baseline fecal calprotectin.

The IBDQ is a 32-item patient completed questionnaire that measures 4 aspects of patients' lives: symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional function, and social function. 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. IBDQ total score is calculated as the sum of all questions. Scores range from 32 to 224; a higher score indicates a better quality of life.

Time frame: Baseline, Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

The Urgency NRS is a single patient-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).

Time frame: Baseline, Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

The Urgency NRS is a single patient-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).

Time frame: Baseline, Week 12

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Clinical remission defined as CDAI total score \<150. The CDAI is an 8- item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter \[hematocrit\]). Total score range of 0 to 600 points.

Time frame: Week 12

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Clinical remission defined as CDAI total score \<150. The CDAI is an 8- item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter \[hematocrit\]). Total score range of 0 to 600 points.

Time frame: Week 52

Population: All randomized participants who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug per protocol.

Clinical response by PRO defined as ≥ 30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe).

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug and had at least one draining cutaneous fistulae at baseline.

Clinical Response by PRO defined as ≥30% decrease in SF and/or AP & neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Clinical Remission by PRO defined as SF≤3 and not worse than baseline (as per Bristol Stool Scale Category 6 or 7) and AP ≤1 and no worse than baseline.

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Clinical response by PRO defined as ≥30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Clinical remission defined as CDAI total score \<150. The CDAI is an 8- item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter \[hematocrit\]). Total score range of 0 to 600 points. Corticosteroid-free clinical remission by CDAI is defined as achieving clinical remission by CDAI at Week 52 and being corticosteroid free from Week 40 to Week 52.

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Clinical Response by PRO defined as ≥30% decrease in SF and/or AP & neither score worse than baseline. SF (number of liquid or very soft stools) per Bristol Stool Scale Category 6 or 7 & AP (4-point scale:0=none,1=mild,2=moderate,3=severe). Endoscopic remission=SES-CD Total Score ≤4 & at least 2-point reduction from baseline & no subscore \>1.SES-CD evaluates 4 endoscopic variables in 5 bowel segments & each of 20 individual variables scored 0-3: presence & size of ulcers (none=0;diameter 0.1-0.5 cm=1;0.5-2 cm=2;\>2 cm=3);extent of ulcerated surface (none=0;\<10%=1;10% to 30%=2;\>30%=3);extent of affected surface (none=0;\<50%=1;50% to 75%=2;\>75%=3);presence & type of narrowing (none=0;single,can be passed=1;multiple,can be passed=2;cannot be passed=3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56;higher scores indicating more severe disease. No subscore \>1=no segmental subscore (sum of the 4 individual variable scores for each of the 5 bowel segments) \>1

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Clinical response by PRO defined as ≥30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe).

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug and had at least one EIM at baseline.

Endoscopic remission is defined as SES-CD Total Score ≤4 and at least a 2-point reduction from baseline and no subscore \>1. SES-CD evaluates 4 endoscopic variables in 5 bowel segments and each of the 20 individual variables is scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; \>2 cm = 3); extent of ulcerated surface (none = 0; \<10% = 1; 10% to 30% = 2; \>30% = 3); extent of affected surface (none = 0; \<50% = 1; 50% to 75% = 2; \>75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed =3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease. No subscore \>1 is defined as no segmental subscore (sum of the 4 individual variable scores for each of the 5 bowel segments) \>1.

Time frame: Week 12

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Endoscopic Response defined as ≥50% reduction from baseline in SES-CD total score. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; \>2 cm = 3); extent of ulcerated surface (none = 0; \<10% = 1; 10% to 30% = 2; \>30% = 3); extent of affected surface (none = 0; \<50% = 1; 50% to 75% = 2; \>75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed = 3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease.

Time frame: Week 12

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Endoscopic Response defined as ≥50% reduction from baseline in SES-CD total score. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; \>2 cm = 3); extent of ulcerated surface (none = 0; \<10% = 1; 10% to 30% = 2; \>30% = 3); extent of affected surface (none = 0; \<50% = 1; 50% to 75% = 2; \>75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed = 3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease.

Time frame: Week 52

Population: All randomized participants who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug per protocol.

Alternate endoscopic remission is defined as SES-CD Total Score ≤4 and at least a 2-point reduction from baseline and no subscore \>1. SES-CD evaluates 4 endoscopic variables in 5 bowel segments and each of the 20 individual variables is scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; \>2 cm = 3); extent of ulcerated surface (none = 0; \<10% = 1; 10% to 30% = 2; \>30% = 3); extent of affected surface (none = 0; \<50% = 1; 50% to 75% = 2; \>75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed =3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease. No subscore \>1 is defined as no subscore \>1 in any of the 20 individual variables.

Time frame: Week 12

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.

Clinical Response by PRO defined as ≥30% decrease in SF and/or AP & neither score worse than baseline. SF (number of liquid or very soft stools) per Bristol Stool Scale Category 6 or 7 & AP (4-point scale:0=none,1=mild,2=moderate,3=severe). Alternate endoscopic remission defined as SES-CD Total Score ≤4 & at least 2-point reduction from baseline & no subscore \>1.SES-CD evaluates 4 endoscopic variables in 5 bowel segments & each of 20 individual variables scored 0-3: presence & size of ulcers (none=0;diameter 0.1-0.5 cm=1;0.5-2 cm=2;\>2 cm=3); extent of ulcerated surface (none=0;\<10%=1;10% to 30%=2;\>30%=3);extent of affected surface (none=0;\<50%=1;50% to 75%=2;\>75%=3); presence & type of narrowing (none=0;single,can be passed=1;multiple,can be passed=2;cannot be passed=3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease. No subscore \>1 is defined as no subscore \>1 in any of the 20 individual variables.

Time frame: Week 12 to Week 52

Population: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.