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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- and Active- Controlled, Treat-Through Study to Evaluate the Efficacy and Safety of Mirikizumab in Patients With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Mirikizumab
* Drug: Mirikizumab
* Drug: Ustekinumab
* Drug: Ustekinumab
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CD for at least 3 months prior to baseline Confirmed diagnosis of moderate to severe CD as assessed by SF, AP score, and SES-CD Demonstrated intolerance, loss of response or inadequate response to conventional or to biologic therapy for CD If female, subject must meet the contraception recommendations Exclusion Criteria: Have a current diagnosis of ulcerative colitis, inflammatory bowel disease-unclassified (IBD-U) (formerly known as indeterminate colitis) or short bowel syndrome Currently have or are suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained, adequately treated and resolved at least 3 weeks prior to baseline or 8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery Have a stoma, ileoanal pouch or ostomy Have had a bowel resection within 6 months, or any kind of intra-abdominal or extra abdominal surgery within 3 months of baseline Have ever received any monoclonal antibodies binding IL-23

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mirikizumab<br>Mirikizumab given intravenously (IV) and subcutaneously (SC). Participants in the open-label adolescent addendum will be given mirikizumab IV and SC. | Drug: Mirikizumab<br>* Administered IV<br>* Other names: LY3074828;Drug: Mirikizumab<br>* Administered SC<br>* Other names: LY3074828;|
| Active Comparator: Ustekinumab<br>Ustekinumab given IV and SC. | Drug: Ustekinumab<br>* Administered IV<br>Drug: Ustekinumab<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Placebo given IV and SC. | Drug: Placebo<br>* Administered IV<br>Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Response at Week 12 and Endoscopic Response at Week 52 | Clinical response by Patient Reported Outcome (PRO) based on stool frequency (SF) and abdominal pain (AP) Endoscopic response based on Simple Endoscopic Score for Crohn's Disease (SES-CD) total score | Baseline to Week 52 | 
| Percentage of Participants Achieving Clinical Response at Week 12 and Clinical Remission at Week 52 | Clinical response by PRO based on SF and AP Clinical remission based on CDAI | Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Endoscopic Response | Endoscopic response based on Simple Endoscopic Score for Crohn's Disease (SES-CD) total score | Week 52 | 
| Percentage of Participants Achieving Clinical Remission | Clinical remission based on Crohn's Disease Activity Index (CDAI) | Week 52 | 
| Percentage of Participants Achieving Endoscopic Response | Endoscopic Response based on SES-CD total score | Week 12 | 
| Percentage of Participants Achieving Endoscopic Remission | Endoscopic remission based on SES-CD total score | Week 12 | 
| Percentage of Participants Achieving Clinical Remission | Clinical remission based on CDAI | Week 12 | 
| Change from Baseline in Urgency Numeric Rating Score (NRS) | Change from Baseline in Urgency NRS | Baseline, Week 12 | 
| Change from Baseline in Urgency NRS | Change from Baseline in Urgency NRS | Baseline, Week 52 | 
| Percentage of Participants Achieving Clinical Response at Week 12 and Clinical Remission by PRO at Week 52 | Clinical Response and Clinical Remission based on PRO | Baseline to Week 52 | 
| Percentage of Participants Achieving Clinical Response at Week 12 and Endoscopic Remission at Week 52 | Clinical Response by PRO and Endoscopic Remission by SES-CD | Baseline to Week 52 | 
| Percentage of Participants Achieving Clinical Response at Week 12 and Corticosteroid-free AND either in Clinical Remission or Endoscopic Remission at Week 52 | Clinical Response by PRO, Clinical remission by CDAI, Endoscopic Remission by SES-CD | Baseline to Week 52 | 
| Change from Baseline in C-Reactive Protein | Change from baseline in C-Reactive Protein | Baseline, Week 52 | 
| Change from Baseline in Fecal Calprotectin | Change from baseline in fecal calprotectin | Baseline, Week 52 | 
| Percentage of Participants with Extraintestinal Manifestations (EIMs) of Crohn's Disease | Percentage of participants with EIMs of Crohn's Disease | Week 52 | 
| Percentage of Participants with Fistulae Response | Percentage of participants with fistulae response | Week 52 | 
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Mirikizumab | PK: AUC of mirikizumab | Baseline through Week 52 | 
| Change from Baseline in Health Related Quality of Life | Health related quality of life based on Inflammatory Bowel Disease Questionnaire (IBDQ) score | Baseline, Week 52 |