The reason for this study is to see if the study drug mirikizumab is safe and effective in participants with moderately to severely active Crohn's disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
1,158
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Response at Week 52 (Placebo and Mirikizumab)
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
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission at Week 52 (Placebo and Mirikizumab)
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
Percentage of Adult Participants Achieving Endoscopic Response at Week 12 (Placebo and Mirikizumab)
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Administered SC
Administered IV
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University of Alabama-The Kirklin Clinic
Birmingham, Alabama, United States
Digestive Health Specialists
Dothan, Alabama, United States
Lakeview Clinical Research
Guntersville, Alabama, United States
Care Access Research - Tuscaloosa
Tuscaloosa, Alabama, United States
Research Solutions of Arizona
Litchfield Park, Arizona, United States
Central Arizona Medical Associates, PC
Mesa, Arizona, United States
Arizona Arthritis & Rheumatology Research, PLLC
Phoenix, Arizona, United States
Reliance Research
Scottsdale, Arizona, United States
Synexus Site Network
Tempe, Arizona, United States
inSite Digestive Health Care
Arcadia, California, United States
...and 570 more locations
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
Percentage of Adult Participants Achieving Endoscopic Response at Week 52
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
Percentage of Adult Participants Achieving Clinical Remission at Week 12 (Placebo and Mirikizumab)
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
Percentage of Adult Participants Achieving Clinical Remission at Week 52
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
Percentage of Adult Participants Achieving Endoscopic Remission at Week 12 (Placebo and Mirikizumab)
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
Change From Baseline in Urgency Numeric Rating Scale (NRS) at Week 12 in Adult Participants (Placebo and Mirikizumab)
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
Change From Baseline in Urgency NRS at Week 52 in Adult Participants (Placebo and Mirikizumab)
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
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission by PRO at Week 52 (Placebo and Mirikizumab)
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
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Remission at Week 52 (Placebo and Mirikizumab)
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
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Corticosteroid-free Clinical Remission at Week 52 (Placebo and Mirikizumab)
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
Change From Baseline in C-Reactive Protein (CRP) at Week 52 in Adult Participants (Placebo and Mirikizumab)
Change from baseline in CRP
Time frame: Baseline, Week 52
Change From Baseline in Fecal Calprotectin at Week 52 in Adult Participants (Placebo and Mirikizumab)
Change from baseline in Fecal Calprotectin
Time frame: Baseline, Week 52
Percentage of Adult Participants Achieving Clinical Response at Week 12 and Resolution of Baseline Extraintestinal Manifestations (EIMs) at Week 52 (Placebo and Mirikizumab)
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
Percentage of Adult Participants Achieving Clinical Response at Week 12 and ≥50% Reduction in Number of Draining Cutaneous Fistulae at Week 52 in Participants With Draining Cutaneous Fistulae at Baseline (Placebo and Mirikizumab)
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
Change From Baseline in Health Related Quality of Life at Week 52 in Adult Participants: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score (Placebo and Mirikizumab)
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
Adult Population Pharmacokinetics (PopPK): Area Under the Concentration Time Curve (AUC) of Mirikizumab
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