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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of guselkumab in participants with moderately to severely active ulcerative colitis (UC).

Detailed Description
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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 study is designed to answer scientific questions pertaining to the efficacy and safety of guselkumab in the treatment of moderately to severely active UC. Overall, the study will evaluate long-term guselkumab treatment. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points.

Official Title
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A Phase 2b/3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Placebo
* Drug: Guselkumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of ulcerative colitis (UC) Moderately to severely active UC, defined by modified Mayo score Demonstrated inadequate response or intolerance to medical therapies specified in the protocol Screening laboratory test results within the parameters specified in the protocol Exclusion Criteria: Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's disease or clinical findings suggestive of Crohn's disease UC limited to the rectum only or to less than (<) 20 centimeter (cm) of the colon Presence of a stoma Presence or history of a fistula Receiving prohibited medications and/or treatment

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction Study 1: Guselkumab Dose 1<br>Participants will receive guselkumab dose 1 intravenously (IV) in Induction Study 1. Subsequent study treatment will be determined by the participant's clinical response status at Week 12. | Drug: Guselkumab<br>* Participants will receive guselkumab IV or SC.<br>|
| Experimental: Induction Study 1: Guselkumab Dose 2<br>Participants will receive guselkumab dose 2 IV in Induction Study 1. Subsequent study treatment will be determined by the participant's clinical response status at Week 12. | Drug: Guselkumab<br>* Participants will receive guselkumab IV or SC.<br>|
| Placebo Comparator: Induction Study 1: Placebo IV<br>Participants will receive matching placebo IV in Induction Study 1. Subsequent study treatment will be determined by the participant's clinical response status at Week 12. Clinical nonresponders will be administered guselkumab IV. | Drug: Placebo<br>* Participants will receive matching placebo IV or SC.<br>|
| Experimental: Induction Study 2: Guselkumab IV<br>Participants will receive guselkumab IV in Induction Study 2. Subsequent study treatment will be determined by the participant's clinical response status at Week 12. | Drug: Guselkumab<br>* Participants will receive guselkumab IV or SC.<br>|
| Placebo Comparator: Induction Study 2: Placebo IV<br>Participants will receive matching placebo IV in Induction Study 2. Subsequent study treatment will be determined by the participant's clinical response status at Week 12. Clinical nonresponders will be administered guselkumab IV. | Drug: Placebo<br>* Participants will receive matching placebo IV or SC.<br>|
| Experimental: Maintenance Study: Maintenance Dose Regimen 1<br>Participants will receive guselkumab maintenance dose regimen 1 subcutaneously (SC) every 4 weeks (q4w). | Drug: Guselkumab<br>* Participants will receive guselkumab IV or SC.<br>|
| Experimental: Maintenance Study: Maintenance Dose Regimen 2<br>Participants will receive guselkumab maintenance dose regimen 2 SC every 8 weeks (q8w). | Drug: Guselkumab<br>* Participants will receive guselkumab IV or SC.<br>|
| Placebo Comparator: Maintenance Study: Placebo SC<br>Participants will receive matching placebo SC q4w. | Drug: Placebo<br>* Participants will receive matching placebo IV or SC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction Study 1: Clinical Response at Week 12 | Clinical response per modified Mayo score. | Week 12 | 
| Induction Study 2: Clinical Remission at Week 12 | Clinical remission per modified Mayo score. | Week 12 | 
| Maintenance Study: Clinical Remission at Week 44 | Clinical remission per modified Mayo score. | Week 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction Study 1: Clinical Remission at Week 12 | Clinical remission per modified Mayo score. | Week 12 | 
| Induction Study 1: Symptomatic Remission at Week 12 | Symptomatic remission per stool frequency and rectal bleeding subscores. | Week 12 | 
| Induction Study 1: Endoscopic Healing at Week 12 | Endoscopic healing per endoscopy subscore. | Week 12 | 
| Induction Study 1: Histo-Endoscopic Mucosal Healing at Week 12 | Histo-endoscopic mucosal healing per endoscopy subscore and histologic grading. | Week 12 | 
| Induction Study 1: Endoscopic Normalization at Week 12 | Endoscopic normalization per endoscopy subscore. | Week 12 | 
| Induction Study 2: Symptomatic Remission at Week 12 | Symptomatic remission per stool frequency and rectal bleeding subscores. | Week 12 | 
| Induction Study 2: Endoscopic Healing at Week 12 | Endoscopic healing per endoscopy subscore. | Week 12 | 
| Induction Study 2: Clinical Response at Week 12 | Clinical response per modified Mayo score. | Week 12 | 
| Induction Study 2: Symptomatic Remission at Week 4 | Symptomatic remission per stool frequency and rectal bleeding subscores. | Week 4 | 
| Induction Study 2: Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week 12 | IBDQ remission is defined as total IBDQ score greater than or equal to (>=) 170. IBDQ is a validated, 32-item, self-reported questionnaire for participants with inflammatory bowel disease (IBD) that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes. | Week 12 | 
| Induction Study 2: Histo-Endoscopic Mucosal Healing at Week 12 | Histo-endoscopic mucosal healing per endoscopy subscore and histologic grading. | Week 12 | 
| Induction Study 2: Fatigue Response at Week 12 | Fatigue response is defined as an improvement from induction baseline in patient-reported outcomes measurement information system (PROMIS)-fatigue short form 7a. The PROMIS Fatigue Short Form 7a contains 7 items evaluating fatigue-related symptoms (that is, tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily activities (that is, activity limitations related to work, self-care, and exercise). PROMIS Fatigue Short Form 7a has a recall period of past 7 days. | Week 12 | 
| Induction Study 2: Symptomatic Remission at Week 2 | Symptomatic remission per stool frequency and rectal bleeding subscores. | Week 2 | 
| Induction Study 2: Endoscopic Normalization at Week 12 | Endoscopic normalization per endoscopy subscore. | Week 12 | 
| Maintenance Study: Symptomatic Remission at Week 44 | Symptomatic remission per stool frequency and rectal bleeding subscores. | Week 44 | 
| Maintenance Study: Endoscopic Healing at Week 44 | Endoscopic healing per endoscopy subscore. | Week 44 | 
| Maintenance Study: Corticosteroid-free Clinical Remission at Week 44 | Corticosteroid-free clinical remission per modified Mayo score. | Week 44 | 
| Maintenance Study: Clinical Response at Week 44 | Clinical response per modified Mayo score. | Week 44 | 
| Maintenance Study: Histo-Endoscopic Mucosal Healing at Week 44 | Histo-endoscopic mucosal healing per endoscopy subscore and histologic grading. | Week 44 | 
| Maintenance Study: IBDQ Remission at Week 44 | IBDQ remission is defined as total IBDQ score >= 170. IBDQ is a validated, 32-item, self-reported questionnaire for participants with IBD that will be used to evaluate the disease-specific health-related quality of life across 4 dimensional scores: bowel symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes. | Week 44 | 
| Maintenance Study: Fatigue Response at Week 44 | Fatigue response is defined as an improvement from induction baseline in PROMIS-fatigue short form 7a. The PROMIS Fatigue Short Form 7a contains 7 items evaluating fatigue-related symptoms (that is, tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily activities (that is, activity limitations related to work, self-care, and exercise). PROMIS Fatigue Short Form 7a has a recall period of past 7 days. | Week 44 | 
| Maintenance Study: Clinical Remission at Week 44 Among the Participants Who had Achieved Clinical Remission at Maintenance Baseline | Clinical remission per modified Mayo score. | Week 44 | 
| Maintenance Study: Endoscopic Normalization at Week 44 | Endoscopic normalization per endoscopy subscore. | Week 44 |