A Study 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 efficacy and safety of JNJ-78934804 as compared to guselkumab and golimumab in participants with moderately to severely active ulcerative colitis who have had an inadequate initial response, loss of response, or intolerance to one or more approved advanced therapy.

Official Title
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A Phase 2b Randomized, Double-blind, Active-and Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Induction and Maintenance 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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* Biological: Guselkumab
* Biological: Golimumab
* Biological: JNJ-78934804
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of ulcerative colitis (UC) for at least 3 months prior to baseline Moderately to severely active UC as assessed by the modified Mayo Score Demonstrated inadequate response, loss of response, or intolerance to at least one biologic or novel oral with biologic-like activity If female and of childbearing potential, must meet the contraception and reproduction requirements Exclusion Criteria: Has severe extensive colitis as defined in the protocol Extent of inflammatory disease limited to the rectum Participants with current diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's disease (CD) Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, sinopulmonary infections, bronchiectasis, recurrent renal/urinary tract infections (example, pyelonephritis, cystitis), an open, draining, or infected skin wound, or an ulcer Currently has a malignancy or a history of malignancy within 5 years before screening (with the exception of nonmelanoma skin cancer or cervical carcinoma in situ that has been treated with no evidence of recurrence within 12 months of first dose of study intervention)

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 |
| --- | --- |
| Placebo Comparator: Group 1: Placebo<br>Participants will receive placebo subcutaneously (SC). All participants who meet inadequate response criteria will be escalated to an active treatment. Participants who are eligible and willing to continue the study intervention that they are receiving at Week 44 may enter the long-term extension. | Drug: Placebo<br>* Placebo will be administered as subcutaneous injection.<br>|
| Experimental: Group 2: Guselkumab<br>Participants will receive guselkumab dose regimen 1 SC. All participants who meet inadequate response criteria will be escalated to an active treatment. Participants who are eligible and willing to continue the study intervention that they are receiving at Week 44 may enter the long-term extension. | Biological: Guselkumab<br>* Guselkumab will be administered as subcutaneous injection.<br>|
| Experimental: Group 3: Golimumab<br>Participants will receive golimumab dose regimen 1 SC. All participants who meet inadequate response criteria will be escalated to an active treatment. Participants who are eligible and willing to continue the study intervention that they are receiving at Week 44 may enter the long-term extension. | Biological: Golimumab<br>* Golimumab will be administered as subcutaneous injection.<br>|
| Experimental: Group 4: JNJ-78934804 (High-dose)<br>Participants will receive JNJ-78934804 dose regimen 1 SC. All participants who meet inadequate response criteria will be escalated to an active treatment. Participants who are eligible and willing to continue the study intervention that they are receiving at Week 44 may enter the long-term extension. | Biological: JNJ-78934804<br>* JNJ-78934804 will be administered subcutaneously as per defined regimen.<br>|
| Experimental: Group 5: JNJ-78934804 (Mid-dose)<br>Participants will receive JNJ-78934804 dose regimen 2 SC. All participants who meet inadequate response criteria will be escalated to an active treatment. Participants who are eligible and willing to continue the study intervention that they are receiving at Week 44 may enter the long-term extension. | Biological: JNJ-78934804<br>* JNJ-78934804 will be administered subcutaneously as per defined regimen.<br>|
| Experimental: Group 6: JNJ-78934804 (Low-dose)<br>Participants will receive JNJ-78934804 dose regimen 3 SC. All participants who meet inadequate response criteria will be escalated to an active treatment. Participants who are eligible and willing to continue the study intervention that they are receiving at Week 44 may enter the long-term extension. | Biological: JNJ-78934804<br>* JNJ-78934804 will be administered subcutaneously as per defined regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Clinical Remission at Week 48 | Percentage of participants with clinical remission at Week 48 will be reported. Clinical remission based on the modified Mayo subscores. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Endoscopic Improvement at Week 48 | Percentage of participants with endoscopic improvement at Week 48 will be reported. Endoscopic improvement at Week 48 based on the Mayo endoscopic subscore. | Week 48 | 
| Percentage of Participants with Symptomatic Remission at Week 48 | Percentage of participants with symptomatic remission at Week 48 will be reported. Symptomatic remission at Week 48 based on stool and rectal bleeding symptoms. | Week 48 | 
| Percentage of Participants with Combination of Histological Remission and Endoscopic Improvement at Week 48 | Percentage of participants with combination of histological remission and endoscopic improvement at Week 48 will be reported. Histologic remission and endoscopic improvement at Week 48 based on the histologic grading and the Mayo endoscopy subscore. | Week 48 | 
| Percentage of Participants with Clinical Remission at Week 24 | Percentage of participants with clinical remission at Week 24 will be reported. Clinical remission based on the modified Mayo subscores | Week 24 | 
| Percentage of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. | Up to Week 48 | 
| Percentage of Participants with Serious Adverse Events (SAEs) | A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important. | Up to Week 48 | 
| Serum Concentrations of Guselkumab Over Time | Serum concentrations of guselkumab over time will be reported. Serum samples will be analyzed to determine concentrations of guselkumab using a validated, specific, and sensitive method. | Up to Week 48 | 
| Serum Concentrations of Golimumab Over Time | Serum concentration of golimumab over time will be reported. Serum samples will be analyzed to determine concentrations of golimumab using a validated, specific, and sensitive method. | Up to Week 48 | 
| Percentage of Participants with Antibodies to Guselkumab | Percentage of participants with antibodies to guselkumab will be reported. | Up to Week 48 | 
| Titers of Antibodies to Guselkumab | Titers of antibodies to guselkumab will be reported. | Up to Week 48 | 
| Percentage of Participants with Antibodies to Golimumab | Percentage of Participants with Antibodies to golimumab will be reported. | Up to Week 48 | 
| Titers of Antibodies to Golimumab | Titers of antibodies to golimumab will be reported. | Up to Week 48 | 
| Percentage of Participants with Neutralizing Antibodies to Guselkumab | Percentage of participants with neutralizing antibodies to guselkumab will be reported. | Up to Week 48 | 
| Percentage of Participants with Neutralizing Antibodies to Golimumab | Percentage of participants with neutralizing antibodies to golimumab will be reported. | Up to Week 48 |