Crohn's Disease
Conditions
Keywords
inflammatory bowel disease, IL-23, biologic
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of the study drug Mirikizumab in participants with active Crohn's Disease.
Interventions
DRUGMirikizumab
DRUGPlacebo
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Active Crohn's Disease (CD) as determined by the SES-CD, and participant reported stool frequency and abdominal pain. * Inadequate response or failure to tolerate at least one of the following: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants (eg, azathioprine, 6-mercaptopurine, or methotrexate); or prior exposure to biologics for the treatment of CD.
Exclusion criteria
* Have complications of CD such as strictures, stenoses, or any other manifestation for which surgery might be indicated, or that could confound the evaluation of efficacy. * Diagnosis of conditions affecting the digestive tract, such as ulcerative colitis, indeterminate colitis, fistulizing disease, abdominal or perianal abscess, adenomatous colonic polyps not excised, colonic mucosal dysplasia, and short bowel syndrome. * Have had any kind of bowel resection, diversion, or placement of a stoma within 6 months or any other intra-abdominal surgery within 3 months prior to screening. * Are unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any reason that may compromise the subject's safety or confound data interpretation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Endoscopic Response at Week 12 | Week 12 | Endoscopic response defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD calculated as sum of 4 variables for 5 bowel segments: (ileum;right,transverse,and left colon;and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; \>2 cm = score 3); extent of ulcerated surface (none = 0; \<10% = 1;10-30% = 2;\>30% = 3);extent of affected surface (none = 0; \<50% = 1;50-75% = 2;\>75% =3); and presence and type of narrowings (none=0; single, can be passed=1; multiple,can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12 | Week 12 | PRO remission is defined as stool frequency (SF) ≤2.5 and abdominal pain (AP) ≤1 and no worse than baseline at week 12. SF captures the number of liquid or very soft stools. AP score is classified as 0=none, 1=mild, 2=moderate, 3=severe. |
| Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12 | Baseline, Week 12 | The PGRS is a 1-item patient-rated questionnaire designed to assess the participant's rating of their disease symptom severity over the past 24 hours. Responses are graded on a 6-point scale in which a score of 1 indicates the subject has no symptoms (that is, none) and a score of 6 indicates that the participant's symptom are very severe. Least Squares Mean (LS Mean) was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors. |
| Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12 | Baseline, Week 12 | The PGRC scale is a patient-rated instrument designed to assess the participant's rating of change in their symptom(s). Responses are graded on a 7-point Likert scale in which a score of 1 indicates that the participant's symptom is very much better, a score of 4 indicates that the participant's symptom has experienced no change, and a score of 7 indicates that the participant's symptom is very much worse. |
| Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12 | Baseline, Week 12 | The IBDQ is a 32-item self-administered questionnaire. The IBDQ has 4 dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). 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 Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors. |
| Percentage of Participants Achieving Endoscopic Remission at Week 12 | Week 12 | Endoscopic remission defined as SES-CD of \<4 ileal-colonic or \<2 for isolated ileal disease, and no subscore \>1 at week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: (ileum; right, transverse, and left colon; and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; greater than (\>) 2 cm = score 3); extent of ulcerated surface (none = 0; less than (\<) 10% = 1; 10-30% = 2; \>30% = 3); extent of affected surface (none = 0; \<50% = 1; 50-75% = 2; \>75% = 3); and presence and type of narrowings (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease. |
| Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | Baseline, Week 12 | The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains:physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors. |
| Population Pharmacokinetics (PopPK): Mean Population Clearance of Mirikizumab | Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion | Population mean (between-subject coefficient variance \[CV %\]) apparent clearance. Clearance is estimated based on concentration data collected in the time frame of 0-208 weeks. |
| Population Pharmacokinetics (PopPK): Mean Population Volume of Distribution of Mirikizumab | Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion | Population mean (between-subject coefficient variance \[CV %\]) apparent volume of distribution. Volume of distribution is estimated based on concentration data collected in the time frame of 0-208 weeks. |
| Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 | Baseline, Week 12 | The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0-4 associated with a range over Not at all to Very much for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors. |
Countries
Australia, Belgium, Canada, Czechia, Hungary, Japan, Netherlands, Poland, Romania, Russia, Switzerland, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Q4W Participants received placebo administered IV Q4W. | 64 |
| 200 mg Mirikizumab IV Q4W Participants received 200 mg mirikizumab administered IV Q4W. | 31 |
| 600 mg Mirikizumab IV Q4W Participants received 600 mg mirikizumab administered IV Q4W. | 32 |
| 1000 mg Mirikizumab IV Q4W Participants received 1000 mg mirikizumab administered IV Q4W. | 64 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Follow-up Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
| Period 1 (Weeks 0 to 12) | Adverse Event | 4 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 to 12) | Enrollment Failure | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 to 12) | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 to 12) | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 to 12) | Sponsor Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 to 12) | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 3 | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | Endoscopic Procedure was not Evaluated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | Lack of Efficacy and Withdrew from Study | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | PI and Sponsor Decision due to Subject Safety | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | PI decision due to Lack of Efficacy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | PI Decision due to Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 12 to 52) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | Decided to not Participate in Extension Period (Week 104-208) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | Non-Compliance With Study Visit Schedule | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | PI Decision as Subject Not Responding to Study Drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | Roll over to AMAX | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 108 | 0 | 0 | 0 | 0 | 0 |
| Period 3 (Weeks 52 to 208) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo IV Q4W | Total | 1000 mg Mirikizumab IV Q4W | 600 mg Mirikizumab IV Q4W | 200 mg Mirikizumab IV Q4W |
|---|---|---|---|---|---|
| Age, Continuous | 39.00 years STANDARD_DEVIATION 13.04 | 38.70 years STANDARD_DEVIATION 12.7 | 37.70 years STANDARD_DEVIATION 13.11 | 40.40 years STANDARD_DEVIATION 13.33 | 38.10 years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 160 Participants | 54 Participants | 26 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 23 Participants | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 20 Participants | 8 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 11 Participants | 4 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 55 Participants | 159 Participants | 52 Participants | 24 Participants | 28 Participants |
| Region of Enrollment Australia | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Belgium | 0 Participants | 6 Participants | 4 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Czechia | 4 Participants | 10 Participants | 5 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Hungary | 3 Participants | 7 Participants | 3 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Japan | 6 Participants | 18 Participants | 7 Participants | 4 Participants | 1 Participants |
| Region of Enrollment Netherlands | 2 Participants | 7 Participants | 2 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Poland | 6 Participants | 24 Participants | 9 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Romania | 0 Participants | 5 Participants | 4 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Russia | 6 Participants | 14 Participants | 3 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Ukraine | 4 Participants | 19 Participants | 6 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 29 Participants | 76 Participants | 20 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Female | 36 Participants | 98 Participants | 30 Participants | 18 Participants | 14 Participants |
| Sex: Female, Male Male | 28 Participants | 93 Participants | 34 Participants | 14 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 31 | 0 / 32 | 0 / 64 | 0 / 9 | 0 / 9 | 0 / 23 | 0 / 46 | 0 / 30 | 0 / 59 | 0 / 136 | 0 / 1 | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 24 / 64 | 11 / 31 | 12 / 32 | 27 / 64 | 7 / 9 | 5 / 9 | 14 / 23 | 30 / 46 | 16 / 30 | 30 / 59 | 89 / 136 | 0 / 1 | 1 / 2 | 1 / 1 | 0 / 1 | 0 / 3 |
| serious Total, serious adverse events | 7 / 64 | 0 / 31 | 3 / 32 | 2 / 64 | 0 / 9 | 0 / 9 | 0 / 23 | 2 / 46 | 3 / 30 | 9 / 59 | 15 / 136 | 0 / 1 | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 3 |
Outcome results
Primary
Percentage of Participants Achieving Endoscopic Response at Week 12
Endoscopic response defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD calculated as sum of 4 variables for 5 bowel segments: (ileum;right,transverse,and left colon;and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; \>2 cm = score 3); extent of ulcerated surface (none = 0; \<10% = 1;10-30% = 2;\>30% = 3);extent of affected surface (none = 0; \<50% = 1;50-75% = 2;\>75% =3); and presence and type of narrowings (none=0; single, can be passed=1; multiple,can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.
Time frame: Week 12
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo IV Q4W | Percentage of Participants Achieving Endoscopic Response at Week 12 | 10.9 percentage of participants |
| 200 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Endoscopic Response at Week 12 | 25.8 percentage of participants |
| 600 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Endoscopic Response at Week 12 | 37.5 percentage of participants |
| 1000 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Endoscopic Response at Week 12 | 43.8 percentage of participants |
p-value: 0.07990% CI: [1.07, 7.08]Regression, Logistic
p-value: 0.00390% CI: [2.01, 12.07]Regression, Logistic
p-value: <0.00190% CI: [2.81, 13.42]Regression, Logistic
Secondary
Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12
The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains:physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time frame: Baseline, Week 12
Population: All randomized participants who had a baseline and at least one post-baseline PCS and MCS value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | PCS | 3.11 score on a scale | Standard Error 0.774 |
| Placebo IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | MCS | 2.34 score on a scale | Standard Error 1.133 |
| 200 mg Mirikizumab IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | MCS | 7.47 score on a scale | Standard Error 1.602 |
| 200 mg Mirikizumab IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | PCS | 4.70 score on a scale | Standard Error 1.096 |
| 600 mg Mirikizumab IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | MCS | 6.52 score on a scale | Standard Error 1.592 |
| 600 mg Mirikizumab IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | PCS | 8.01 score on a scale | Standard Error 1.108 |
| 1000 mg Mirikizumab IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | PCS | 6.70 score on a scale | Standard Error 0.787 |
| 1000 mg Mirikizumab IV Q4W | Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12 | MCS | 6.05 score on a scale | Standard Error 1.152 |
Comparison: Mental Component Summary (MCS)p-value: 0.00890% CI: [1.95, 8.32]Mixed Models Analysis
Comparison: Mental Component Summary (MCS)p-value: 0.03390% CI: [0.96, 7.41]Mixed Models Analysis
Comparison: Mental Component Summary (MCS)p-value: 0.02190% CI: [1.08, 6.34]Mixed Models Analysis
Comparison: Physical Component Summary (PCS)p-value: 0.22990% CI: [-0.59, 3.77]Mixed Models Analysis
Comparison: Physical Component Summary (PCS)p-value: <0.00190% CI: [2.67, 7.14]Mixed Models Analysis
Comparison: Physical Component Summary (PCS)p-value: 0.00190% CI: [1.81, 5.38]Mixed Models Analysis
Secondary
Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0-4 associated with a range over Not at all to Very much for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time frame: Baseline, Week 12
Population: All randomized participants who had a baseline and at least one post-baseline FACIT-F value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV Q4W | Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 | 2.90 score on a scale | Standard Error 1.209 |
| 200 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 | 10.81 score on a scale | Standard Error 1.728 |
| 600 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 | 9.09 score on a scale | Standard Error 1.721 |
| 1000 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 | 9.62 score on a scale | Standard Error 1.223 |
p-value: <0.00190% CI: [4.48, 11.34]Mixed Models Analysis
p-value: 0.00490% CI: [2.72, 9.67]Mixed Models Analysis
p-value: <0.00190% CI: [3.94, 9.51]Mixed Models Analysis
Secondary
Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12
The IBDQ is a 32-item self-administered questionnaire. The IBDQ has 4 dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). 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 Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time frame: Baseline, Week 12
Population: All randomized participants who had a baseline and at least one post-baseline IBDQ value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV Q4W | Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12 | 17.11 score on a scale | Standard Error 3.725 |
| 200 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12 | 41.16 score on a scale | Standard Error 5.311 |
| 600 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12 | 46.57 score on a scale | Standard Error 5.244 |
| 1000 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12 | 42.35 score on a scale | Standard Error 3.77 |
p-value: <0.00190% CI: [13.53, 34.56]Mixed Models Analysis
p-value: <0.00190% CI: [18.84, 40.08]Mixed Models Analysis
p-value: <0.00190% CI: [16.67, 33.82]Mixed Models Analysis
Secondary
Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12
The PGRS is a 1-item patient-rated questionnaire designed to assess the participant's rating of their disease symptom severity over the past 24 hours. Responses are graded on a 6-point scale in which a score of 1 indicates the subject has no symptoms (that is, none) and a score of 6 indicates that the participant's symptom are very severe. Least Squares Mean (LS Mean) was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time frame: Baseline, Week 12
Population: All randomized participants who had a baseline and at least one post-baseline PGRS value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV Q4W | Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12 | -0.44 score on a scale | Standard Error 0.132 |
| 200 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12 | -1.08 score on a scale | Standard Error 0.194 |
| 600 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12 | -1.27 score on a scale | Standard Error 0.189 |
| 1000 mg Mirikizumab IV Q4W | Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12 | -0.98 score on a scale | Standard Error 0.134 |
p-value: 0.00790% CI: [-1.03, -0.25]Mixed Models Analysis
p-value: <0.00190% CI: [-1.21, -0.45]Mixed Models Analysis
p-value: 0.00590% CI: [-0.84, -0.22]Mixed Models Analysis
Secondary
Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12
The PGRC scale is a patient-rated instrument designed to assess the participant's rating of change in their symptom(s). Responses are graded on a 7-point Likert scale in which a score of 1 indicates that the participant's symptom is very much better, a score of 4 indicates that the participant's symptom has experienced no change, and a score of 7 indicates that the participant's symptom is very much worse.
Time frame: Baseline, Week 12
Population: All randomized participants who had a baseline and at least one post-baseline PGRC value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV Q4W | Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12 | 3.6 score on a scale | Standard Deviation 1.11 |
| 200 mg Mirikizumab IV Q4W | Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12 | 2.8 score on a scale | Standard Deviation 1.26 |
| 600 mg Mirikizumab IV Q4W | Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12 | 2.6 score on a scale | Standard Deviation 0.97 |
| 1000 mg Mirikizumab IV Q4W | Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12 | 2.5 score on a scale | Standard Deviation 0.89 |
Secondary
Percentage of Participants Achieving Endoscopic Remission at Week 12
Endoscopic remission defined as SES-CD of \<4 ileal-colonic or \<2 for isolated ileal disease, and no subscore \>1 at week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: (ileum; right, transverse, and left colon; and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; greater than (\>) 2 cm = score 3); extent of ulcerated surface (none = 0; less than (\<) 10% = 1; 10-30% = 2; \>30% = 3); extent of affected surface (none = 0; \<50% = 1; 50-75% = 2; \>75% = 3); and presence and type of narrowings (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.
Time frame: Week 12
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo IV Q4W | Percentage of Participants Achieving Endoscopic Remission at Week 12 | 1.6 percentage of participants |
| 200 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Endoscopic Remission at Week 12 | 6.5 percentage of participants |
| 600 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Endoscopic Remission at Week 12 | 15.6 percentage of participants |
| 1000 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Endoscopic Remission at Week 12 | 20.3 percentage of participants |
p-value: 0.24190% CI: [0.55, 33.58]Regression, Logistic
p-value: 0.03290% CI: [1.76, 70.64]Regression, Logistic
p-value: 0.00990% CI: [2.82, 91.32]Regression, Logistic
Secondary
Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12
PRO remission is defined as stool frequency (SF) ≤2.5 and abdominal pain (AP) ≤1 and no worse than baseline at week 12. SF captures the number of liquid or very soft stools. AP score is classified as 0=none, 1=mild, 2=moderate, 3=severe.
Time frame: Week 12
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo IV Q4W | Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12 | 6.3 percentage of participants |
| 200 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12 | 12.9 percentage of participants |
| 600 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12 | 28.1 percentage of participants |
| 1000 mg Mirikizumab IV Q4W | Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12 | 21.9 percentage of participants |
p-value: 0.3390% CI: [0.62, 6.45]Regression, Logistic
p-value: 0.00690% CI: [2.02, 16.21]Regression, Logistic
p-value: 0.02990% CI: [1.37, 9.07]Regression, Logistic
Secondary
Population Pharmacokinetics (PopPK): Mean Population Clearance of Mirikizumab
Population mean (between-subject coefficient variance \[CV %\]) apparent clearance. Clearance is estimated based on concentration data collected in the time frame of 0-208 weeks.
Time frame: Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV Q4W | Population Pharmacokinetics (PopPK): Mean Population Clearance of Mirikizumab | 0.0225 Liters per Hour (L/h) | Geometric Coefficient of Variation 30 |
Secondary
Population Pharmacokinetics (PopPK): Mean Population Volume of Distribution of Mirikizumab
Population mean (between-subject coefficient variance \[CV %\]) apparent volume of distribution. Volume of distribution is estimated based on concentration data collected in the time frame of 0-208 weeks.
Time frame: Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV Q4W | Population Pharmacokinetics (PopPK): Mean Population Volume of Distribution of Mirikizumab | 5.05 Liters (L) | Geometric Coefficient of Variation 18 |