An Efficacy and Safety Study of Golimumab in Participants With Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects (good and bad) of golimumab (CNTO 148) therapy in participants with active ulcerative colitis (UC) (sores in the colon).

Detailed Description
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This is a randomized (study medication assigned by chance), double-blind (neither the Physician nor the participant know about the study medication), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions [treatments]) study to evaluate an appropriate intravenous (through a vein in the arm) golimumab induction dose and to demonstrate the safety and efficacy of intravenous induction dosing with golimumab in participants with moderately to severely active UC. At Week 6, participants will be asked to participate in an additional 1-year maintenance study. Participants not entering the 1-year golimumab maintenance study will be evaluated for safety at Week 16. The duration of study will be 6 weeks for participants who enter the 1-year golimumab maintenance study and 16 weeks for participant who do not enter the 1-year golimumab maintenance study.There are 2 parts in this study. Part 1 is Phase 2 dose-ranging portion of study. Participants enrolled in Part 1, will receive a single intravenous infusion of either matching placebo for golimumab or 1 milligram (mg) per kilogram(kg), 2 mg per kg or 4 mg per kg of golimumab. Part 2 of the study is called dose-confirming and newly enrolled participants will receive same doses studied in Part 1, until the doses for Part 2 are selected and Phase 3 begins. At the time that the final doses are selected, all newly enrolled participants will receive 1 of the selected doses or matching placebo; this is the start of the Phase 3 portion of the study. Participants will primarily be assessed using Mayo Score (it is a score developed for measuring disease activity). Participants' safety and quality of life will also be monitored throughout the study.

Official Title
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A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Intravenously, in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Other: Placebo
* Drug: Golimumab 1 mg per kg
* Drug: Golimumab 2 mg per kg
* Drug: Golimumab 4 mg per kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed with moderately to severely active ulcerative colitis (UC) defined by a Mayo score of 6 to 12 inclusive at Baseline (Week 0), including an endoscopic (examination of an internal part of the body with a lighted tube; looking at a part of the body with a lighted tube) subscore of greater than or equal to 2 Participants must have biopsy results (collected at the screening endoscopy (procedure or obtained within the last year) consistent with the diagnosis of UC Participants either currently receiving treatment with, or have a history of failure to respond to, or tolerate, at least 1 of the following therapies: oral 5-aminosalicylate (5-ASAs), oral corticosteroids, 6-mercaptopurine (6-MP) and azathioprine (AZA) Participants with current dependency or with a history of corticosteroid dependency (i.e. an inability to successfully taper corticosteroids without a return of the symptoms of UC) - Not have a diagnosis of active TB Exclusion Criteria: Participants with previous exposure to biologic anti-tumor necrosis factor (TNF) agents Participants with severe extensive UC that is likely to require a colectomy (surgery to remove part or all of the colon) within 12 weeks of study entry Participants having UC limited to the rectum only or to less than 20 centimeter (cm) of the colon Presence of a stoma (an artificial permanent opening especially in the abdominal wall made in surgical procedures) or presence of a fistula Participants with a history of extensive colonic resection

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo for golimumab, intravenous (IV) (through a vein in the arm) infusion administered at Week 0 | Other: Placebo<br>* Matching placebo for golimumab, intravenous infusion administered at Week 0<br>|
| Experimental: Golimumab 1 milligram (mg) per kilogram (kg)<br>Golimumab 1 mg per kg intravenous (IV) infusion administered at Week 0. | Drug: Golimumab 1 mg per kg<br>* Golimumab 1 mg per kg intravenous (IV) infusion administered at Week 0<br>* Other names: CNTO 148;|
| Experimental: Golimumab 2 mg per kg<br>Golimumab 2 mg per kg intravenous (IV) infusion administered at Week 0. | Drug: Golimumab 2 mg per kg<br>* Golimumab 2 mg per kg intravenous (IV) infusion administered at Week 0<br>* Other names: CNTO 148;|
| Experimental: Golimumab 4 mg per kg<br>Golimumab 4 mg per kg, intravenous (IV) infusion administered at Week 0. | Drug: Golimumab 4 mg per kg<br>* Golimumab 4 mg per kg intravenous (IV) infusion at Week 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response | Clinical response is defined as decrease from baseline in Mayo score by greater than or equal to 30 percent and greater than or equal to 3, with either a decrease from baseline in rectal bleeding sub-score of greater than or equal to 1 or a rectal bleeding sub-score of 0 or 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and a physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12. | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Remission | Clinical remission is defined as a Mayo score of less than or equal to 2, with no individual sub-score greater than 1. The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings, and a physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12. | Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colitis, ulcerative, Golimumab, CNTO 148