A Study of Efficacy and Safety of Combination Therapy With Guselkumab and Golimumab 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 clinical efficacy and safety of combination therapy with guselkumab and golimumab in participants with moderately to severely active ulcerative colitis (UC).

Official Title
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A Phase 2a Randomized, Double-blind, Active-controlled, Parallel-group, Multicenter, Proof-of-concept Clinical Study to Evaluate the Efficacy and Safety of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Guselkumab Dose 1
* Drug: Guselkumab Dose 2
* Drug: Golimumab Dose 1
* Drug: Golimumab Dose 2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed clinical diagnosis of ulcerative colitis (UC) at least 3 months before screening Moderately to severely active UC as defined by Mayo score History of inadequate response to or failure to tolerate conventional therapy Has screening laboratory test results within the study protocol defined parameters A woman of childbearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin) pregnancy test result at screening and a negative urine pregnancy test result at Week 0 Exclusion Criteria: Has severe extensive colitis as defined in the study protocol Has UC limited to the rectum only or to less than (<) 20 centimeter (cm) of the colon Has a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening Has any known malignancy or has a history of malignancy (with the exception of basal cell carcinoma; squamous cell carcinoma in situ of the skin; or cervical carcinoma in situ that has been treated with no evidence of recurrence; or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years before screening) Has known allergies, hypersensitivity, or intolerance to guselkumab or golimumab or their excipients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Combination Therapy<br>Participants will receive guselkumab Dose 1 as intravenous (IV) infusion and Dose 2 as subcutaneous (SC) injection; and golimumab Dose 1 and Dose 2 as SC injection and placebo to maintain the blind. | Drug: Guselkumab Dose 1<br>* Guselkumab Dose 1 will be administered as IV infusion.<br>Drug: Guselkumab Dose 2<br>* Guselkumab Dose 2 will be administered as SC injection.<br>Drug: Golimumab Dose 1<br>* Golimumab Dose 1 will be administered as SC injection.<br>Drug: Golimumab Dose 2<br>* Golimumab Dose 2 will be administered as SC injection.<br>Drug: Placebo<br>* Placebo will be administered.<br>|
| Experimental: Monotherapy: Guselkumab<br>Participants will receive guselkumab Dose 1 as IV infusion, Dose 2 as SC injection and placebo to maintain the blind. | Drug: Guselkumab Dose 1<br>* Guselkumab Dose 1 will be administered as IV infusion.<br>Drug: Guselkumab Dose 2<br>* Guselkumab Dose 2 will be administered as SC injection.<br>Drug: Placebo<br>* Placebo will be administered.<br>|
| Active Comparator: Monotherapy: Golimumab<br>Participants will receive golimumab Dose 1 and Dose 2 as SC injection and placebo to maintain the blind. | Drug: Golimumab Dose 1<br>* Golimumab Dose 1 will be administered as SC injection.<br>Drug: Golimumab Dose 2<br>* Golimumab Dose 2 will be administered as SC injection.<br>Drug: Placebo<br>* Placebo will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combination Phase: Percentage of Participants Who Achieved Clinical Response at Week 12 | Clinical response was defined as a decrease from baseline in the Mayo score greater than or equal to (>=) 30 percent (%) and >=3 points with either a decrease from baseline in the rectal bleeding subscore (RBS) >=1 or a RBS of 0 or 1. The Mayo score was calculated as the sum of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings - each with score range of 0 (normal activity) to 3 (severe activity) and a total score range of 0 to 12 points. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease. Higher scores indicate more severity. This outcome measure was analyzed for combination phase only as preplanned in the protocol. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combination Phase: Percentage of Participants Who Achieved Clinical Remission at Week 12 | Clinical remission was defined as the Mayo score less than or equal to (<=) 2 with no individual subscore greater than (>) 1. The Mayo score was calculated as the sum of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each with score range of 0 (normal activity) to 3 (severe activity) and a total score range of 0 to 12 points. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease. Higher scores indicate more severity. This outcome measure was analyzed for combination phase only as preplanned in the protocol. | Week 12 |