A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Participants With Moderate to Severe Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of vixarelimab compared with placebo in participants with moderate to severe UC who have demonstrated inadequate response to, loss of response to, or intolerance to prior conventional or advanced therapy.

Detailed Description
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This study consists of two periods: An induction period which will test the induction of clinical remission; An optional active treatment extension (ATE) period which will explore durability of clinical response and remission in which all participants will receive vixarelimab.

Official Title
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A Phase II, Multicenter Induction Study With an Active Treatment Extension to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Patients With Moderate to Severe Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Vixarelimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of UC for at least 3 months Moderately to severely active UC, assessed by mMS Inadequate response, loss of response to, or intolerance to conventional or advanced therapies for UC Exclusion Criteria: Diagnosis of Crohn's disease or indeterminate colitis Suspicion of ischemic, radiation, microscopic, or infectious colitis Prior colectomy Prior treatment with systemic janus kinase (JAK) inhibitors

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vixarelimab Dose Regimen 1<br>Participants will receive vixarelimab subcutaneously (SC) during the induction period and the optional ATE period. | Drug: Vixarelimab<br>* Vixarelimab will be administered as per the schedule specified in the respective arms.<br>* Other names: RO7622888; KPL-716;|
| Experimental: Vixarelimab Dose Regimen 2<br>Participants will receive vixarelimab SC during the induction period and the optional ATE period. | Drug: Vixarelimab<br>* Vixarelimab will be administered as per the schedule specified in the respective arms.<br>* Other names: RO7622888; KPL-716;|
| Placebo Comparator: Placebo<br>Participants will receive placebo SC during the induction period and vixarelimab SC during the optional ATE period. | Drug: Vixarelimab<br>* Vixarelimab will be administered as per the schedule specified in the respective arms.<br>* Other names: RO7622888; KPL-716;Drug: Placebo<br>* Vixarelimab matching placebo will be administered as per the schedule specified in the respective arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Clinical Remission | Clinical remission is defined as the Modified Mayo Score (mMS) of ≤ 2, including stool frequency subscore of ≤ 1, rectal bleeding subscore of 0, and endoscopy subscore of ≤ 1. The mMS is a composite of stool frequency, rectal bleeding, and endoscopy with each component having a scoring range of 0-3. The mMS has a total score range of 0-9 with higher scores indicating greater disease severity. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Clinical Response | Clinical response is defined as decrease from baseline in the mMS by ≥2 and ≥ 30% reduction from baseline, with either a decrease of ≥1 in the rectal bleeding subscore or an absolute rectal bleeding subscore of ≤1. The mMS is a composite of stool frequency, rectal bleeding, and endoscopy with each component having a scoring range of 0-3. The mMS has a total score range of 0-9 with higher scores indicating greater disease severity. | Week 12 | 
| Proportion of Participants with Endoscopic Improvement | Endoscopic improvement is defined as a Mayo endoscopy subscore of ≤ 1. Mayo endoscopy subscore has a score range of 0 (normal appearance of mucosa) to 3 (severe disease). | Week 12 | 
| Proportion of Participants with Endoscopic Remission | Endoscopic remission is defined as a Mayo endoscopy subscore of 0. Mayo endoscopy subscore has a score range of 0 (normal appearance of mucosa) to 3 (severe disease). | Week 12 | 
| Number of Participants With Adverse Events (AE) by Severity | The AEs will be graded according to the Division of AIDS (DAIDS) table for grading the severity. The toxicity level is graded from grade 1 (lowest toxicity) to 4 (highest toxicity). | Up to Week 56 | 
| Serum Concentration of Vixarelimab |  | Up to Week 56 | 
| Proportion of Participants With Anti-drug Antibodies (ADAs) to Vixarelimab |  | Up to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease, Gastrointestinal Disease, Ulcerative Colitis, Colitis