An Efficacy and Safety Study of Golimumab (CNTO 148) 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 assess the effects (good and bad) of golimumab (CNTO 148) therapy in participants with ulcerative colitis (UC).

Detailed Description
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This is a multi-center (conducted in more than one center), randomized (study medication assigned by chance), double-blind (neither the physician nor the participant know about the study medication), placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different interventions) study to evaluate the safety and efficacy of golimumab in participants with moderately to severely active UC. There are 2 parts in this study. Part 1 is Phase 2 dose-ranging portion of study. Participants enrolled in Part 1, will receive subcutaneous (under the skin by way of a needle) injections of placebo, golimumab 100 milligram (mg), 200 mg, or 400 mg at Week 0, followed by subcutaneous injections of placebo, golimumab 50 mg, 100 mg, or 200 mg respectively at Week 2. Part 2 is Phase 3 dose-confirming portion of study and newly enrolled participants will receive same doses studied in Part 1, until the doses for Part 2 are selected. At the time that the final doses are selected, all newly enrolled participants will receive 1 of the selected doses or matching placebo. 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 16 weeks after last administration of study agent. The duration of study will be 6 weeks for participants who enter the 1-year golimumab maintenance study and 16 weeks after last administration of study agent for participants who do not enter the 1-year golimumab maintenance study. Efficacy of the participants will primarily be evaluated by clinical response at Week 6. Participants' safety will 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 Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Biological: Placebo
* Biological: Golimumab 100 mg
* Biological: Golimumab 200 mg
* Biological: Golimumab 400 mg
* Biological: Golimumab 50 mg


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, oral corticosteroids, 6-mercaptopurine and azathioprine 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 tuberculosis Participants with negative stool test for enteric (by way of the intestines) pathogens Exclusion Criteria: Participants with prior 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 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2. | Biological: Placebo<br>* Placebo subcutaneous injection (given under the skin by way of a needle) matching to golimumab administered at Week 0 and Week 2.<br>|
| Experimental: Golimumab 100 mg -> 50 mg<br>Golimumab 100 milligram (mg) subcutaneous injection administered at Week 0 and dose is decreased to 50 mg at Week 2. | Biological: Golimumab 100 mg<br>* Golimumab 100 mg subcutaneous injection administered at Week 0 for Golimumab 100 mg -> 50 mg arm group and at Week 2 for Golimumab 200 mg -> 100 mg arm group.<br>Biological: Golimumab 50 mg<br>* Golimumab 50 mg subcutaneous injection administered at Week 2 for Golimumab 100 mg -> 50 mg arm group.<br>|
| Experimental: Golimumab 200 mg -> 100 mg<br>Golimumab 200 mg subcutaneous injection administered at Week 0 and dose is decreased to 100 mg at Week 2. | Biological: Golimumab 100 mg<br>* Golimumab 100 mg subcutaneous injection administered at Week 0 for Golimumab 100 mg -> 50 mg arm group and at Week 2 for Golimumab 200 mg -> 100 mg arm group.<br>Biological: Golimumab 200 mg<br>* Golimumab 200 mg subcutaneous injection administered at Week 0 for Golimumab 200 mg -> 100 mg arm group and at Week 2 for Golimumab 400 mg -> 200 mg arm group.<br>|
| Experimental: Golimumab 400 mg -> 200 mg<br>Golimumab 400 mg subcutaneous injection administered at Week 0 and dose is decreased to 200 mg at Week 2. | Biological: Golimumab 200 mg<br>* Golimumab 200 mg subcutaneous injection administered at Week 0 for Golimumab 200 mg -> 100 mg arm group and at Week 2 for Golimumab 400 mg -> 200 mg arm group.<br>Biological: Golimumab 400 mg<br>* Golimumab 400 mg subcutaneous injection administered at Week 0 for Golimumab 400 mg -> 200 mg arm group.<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 at Week 6 | 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 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. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Remission at Week 6 | 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 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 | 
| Number of Participants With Mucosal Healing at Week 6 | Mucosal healing is determined from the endoscopy sub-score of the Mayo score. Mucosal healing is defined as an endoscopy sub-score of 0 or 1. Higher score indicates higher severity of disease. Endoscopy sub-score ranges from 0 (normal or inactive disease) to 3 (severe disease; spontaneous bleeding and ulceration). | Week 6 | 
| Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 6 | The IBDQ is used to measure disease specific quality of life on a 32 Likert-scaled items questionnaire. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function and social function with scores ranging from 10 to 70, 5 to 35, 12 to 84 and 5 to 35 respectively and the total score ranges from 32 to 224. Higher scores indicate better health related quality of life. | Baseline to 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