A Study of Guselkumab Therapy in Participants With Moderately to Severely Active Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy, including clinical remission of guselkumab subcutaneous (SC) induction compared to placebo in participants with moderately to severely active ulcerative colitis (UC).

Detailed Description
-----------------
UC is a chronic disease of the large intestine, in which the lining of the colon becomes inflamed and develops ulcers. Guselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody (mAb) that binds to human interleukin (IL)-23 with high affinity. The primary hypothesis of this study is that guselkumab SC induction is superior to placebo SC in achieving clinical remission at Week 12 among participants with moderately to severely active UC. This study consists of screening period, main treatment period, extension treatment period and safety follow-up period. Efficacy and safety assessments including adverse events, clinical laboratory tests, vital signs, and physical examinations will be performed according to the schedule of activities. The overall study duration will be up to 112 weeks.

Official Title
-----------------
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction Therapy in Participants With Moderately to Severely Active Ulcerative Colitis

Conditions
-----------------
Colitis, Ulcerative

Intervention / Treatment
-----------------
* Drug: Guselkumab Dose 1
* Drug: Guselkumab Dose 2
* Drug: Guselkumab Dose 3
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent form 18 years of age or older Documented diagnosis of ulcerative colitis (UC) at least 12 weeks prior to screening Moderately to severely active UC as per the modified Mayo score Demonstrated inadequate response to or intolerance of conventional therapy and/or advanced therapy as defined in the protocol Exclusion Criteria: Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's disease Surgery within 8 weeks before screening or planned surgery during the study that may confound the evaluation of benefit from study intervention Receiving prohibited medications and treatments UC limited to the rectum only Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) corona virus disease (COVID-19) infection

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Guselkumab<br>Participants will receive guselkumab (Dose 1) subcutaneous (SC) injection followed by guselkumab (Dose 2) SC injection. | Drug: Guselkumab Dose 1<br>* Guselkumab (Dose 1) will be administered as SC injection.<br>Drug: Guselkumab Dose 2<br>* Guselkumab (Dose 2) will be administered as SC injection.<br>|
| Experimental: Group 2: Guselkumab<br>Participants will receive guselkumab (Dose 1) SC injection followed by guselkumab (Dose 3) SC injection. | Drug: Guselkumab Dose 1<br>* Guselkumab (Dose 1) will be administered as SC injection.<br>Drug: Guselkumab Dose 3<br>* Guselkumab (Dose 3) will be administered as SC injection.<br>|
| Placebo Comparator: Group 3: Placebo<br>Participants will receive matching placebo SC injection. | Other: Placebo<br>* Placebo will be administered as SC injection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Clinical remission per modified Mayo score. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic Remission | Symptomatic remission per Mayo score is defined as a stool frequency subscore of 0 (normal number of stools) or 1 (1 to 2 stools more than normal) and a rectal bleeding subscore of 0 (no blood seen). | Weeks 12 and 24 | 
| Endoscopic Improvement | Endoscopic improvement per Mayo endoscopy subscore. | Weeks 12 and 24 | 
| Clinical Response | Clinical response per modified Mayo score. | Weeks 12 and 24 | 
| Clinical Remission | Clinical remission per modified Mayo score. | Week 24 | 
| Histologic-Endoscopic Mucosal Improvement | Histologic-endoscopic mucosal improvement is defined as a combination of histologic improvement according to the Geboes grading system and endoscopic improvement (Mayo endoscopy subscore of 0 or 1 without friability). | Week 12 | 
| Percentage of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation of Study Intervention | Percentage of participants with AEs, SAEs and AEs leading to discontinuation of study intervention will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to Week 112 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Guselkumab, Colitis, Ulcerative