A Study of Mirikizumab (LY3074828) in Participants With Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if study drug mirikizumab is safe and effective compared to vedolizumab and placebo in participants with moderately to severely active ulcerative colitis (UC).

Official Title
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A Phase 3b, Randomized, Double-Blind, Parallel-Arm, Placebo- and Active- Controlled Treat-Through Study of Mirikizumab and Vedolizumab in Participants With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Mirikizumab IV
* Drug: Mirikizumab SC
* Drug: Vedolizumab IV
* Drug: Placebo IV
* Drug: Placebo SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a diagnosis of UC for at least 3 months prior to baseline Participants must have a confirmed diagnosis of moderately or severely active UC, as assessed by the modified Mayo score (MMS) Participants must have demonstrated an inadequate response to, a loss of response to, or an intolerance to conventional or to biologic therapy for UC Participants must, if female, meet the contraception requirements Exclusion Criteria: Participants must not have a current diagnosis of Crohn's disease or inflammatory bowel disease-unclassified (indeterminate colitis) Participants must not have had a previous colectomy Participants must not have current evidence of toxic megacolon Participants must not have prior exposure to anti-IL-23p19 antibodies (e.g. risankizumab, brazikumab, guselkumab or tildrakizumab), vedolizumab, or natalizumab Participants must not have prior clinical failure or intolerance to anti-IL12p40 antibodies (e.g. ustekinumab), anti-integrin antibodies other than vedolizumab and natalizumab (e.g. etrolizumab) or anti-integrin ligand antibodies (e.g. ontamalimab) within 4 weeks prior to screening endoscopy

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mirikizumab<br>Mirikizumab administered intravenously (IV) and subcutaneously (SC). | Drug: Mirikizumab IV<br>* Administered IV<br>* Other names: LY3074828;Drug: Mirikizumab SC<br>* Administered SC<br>* Other names: LY3074828;|
| Active Comparator: Vedolizumab<br>Vedolizumab administered IV. | Drug: Vedolizumab IV<br>* Administered IV<br>|
| Placebo Comparator: Placebo<br>Placebo administered SC and IV. | Drug: Placebo IV<br>* Administered IV<br>Drug: Placebo SC<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 in Histologic Remission | Histologic remission based on histology. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Symptomatic Remission | Symptomatic remission based on modified Mayo Score (MMS) stool frequency (SF) and rectal bleeding (RB) subscores. | Week 52 | 
| Percentage of Participants in Clinical Remission | Clinical remission based on MMS. | Week 52 | 
| Percentage of Participants in Endoscopic Remission | Endoscopic remission based on MMS ES. | Week 52 | 
| Percentage of Participants with Clinical Response | Clinical response based on MMS. | Week 12 | 
| Percentage of Participants with Corticosteroid (CS) Free Remission without Surgery (Subgroup of Participants on CS at Baseline) | CS free remission without surgery based on clinical remission, symptomatic remission and no CS use. | Week 52 | 
| Percentage of Participants with Resolution of Extraintestinal Manifestations (EIMs) Among Those That had Them at Baseline | Percentage of participants with resolution of EIMs among those that had them at baseline. | Week 52 | 
| Change from Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score | Change from baseline on the IBDQ score. | Baseline, Week 52 | 
| Percentage of Participants Undergoing Surgery for UC (Including Colectomy) | Percentage of participants undergoing surgery for UC (including colectomy). | Week 52 | 
| Percentage of Participants Hospitalized for UC | Percentage of participants hospitalized for UC. | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interleukin-23 (IL-23) antibody, IL-23p19