A Safety and Effectiveness Study of Golimumab in Japanese Patients 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 safety and effectiveness of golimumab in Japanese participants with moderately to severely active ulcerative colitis.

Detailed Description
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This is a double-blind (neither physician nor participant knows the treatment that the participant receives), placebo-controlled (study in which an inactive substance is given to one group of participants, while the study medication is given to another group), multicenter (study conducted at multiple sites), 2-arm (two groups), parallel-group (each group of participants will be treated at the same time), randomized-withdrawal (participants receiving study medication for a specified time will be later randomized to receive either study medication or placebo.) study, including an open-label (all people know the identity of the intervention) induction phase. Approximately 200 participants will participate in this study. This study will consist of an induction phase, a maintenance phase, and a follow-up phase. During the induction phase (lasting 6 weeks) participants will receive 200 mg subcutaneous (SC) (under the skin) golimumab at Week 0 and 100 mg SC golimumab at Week 2. During the maintenance phase (up to Week 52) all participants who show a clinical response (measure of therapeutic effect of study medication) to golimumab during the induction phase will be randomly allocated in a 1:1 ratio to receive either SC administration of placebo (Group 1) or 100 mg golimumab (Group 2) every 4 weeks from Week 0 to Week 52. Participants who do not show clinical response to golimumab will also receive 100 mg SC administration of golimumab until Week 4 and if, by Week 8 of the maintenance phase, these participant's disease activity does not appear to be improving, participants will be discontinued from further study medication administration and will be followed up for safety evaluations 16 weeks after the last administration of study medication. However, if disease activity of these participants improves at Week 8, they will continue to receive golimumab (100 mg every 4 weeks) through Week 52 of the maintenance phase. The follow-up phase will be of 16 weeks duration. During this study, any participant who have a clinical response during the induction phase but lose clinical response at any time will be eligible for dose adjustment only once as follows: 1) participants receiving placebo (Group 1) will receive golimumab 100 mg; 2) participants receiving golimumab 100 mg (Group 2) will continue to receive golimumab 100 mg. Safety evaluations will include assessment of adverse events, laboratory measurements, antinuclear antibodies/anti-double-stranded deoxyribonucleic acid antibodies, and vital signs. The maximum study duration for a participant will be 68 weeks.

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

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Golimumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with ulcerative colitis diagnosed prior to screening Participants should have current treatment for ulcerative colitis with at least one of the following therapies: oral 5-aminosalicylates (5-ASAs), oral corticosteroids, 6-mercaptopurine (6-MP), or azathioprine (AZA) Participants must have a history of failure to respond to, or tolerate, at least 1 of the following therapies: oral 5-ASAs, oral corticosteroids, 6-MP, or AZA Participants must be ambulatory and have moderately to severely active ulcerative colitis confirmed during the screening sigmoidoscopy by a greater than or equal to 2 using the endoscopy subscore of the Mayo score Participants must have moderately to severely active ulcerative colitis, defined as a baseline Mayo score of 6 to 12, inclusive Exclusion Criteria: Participants with ulcerative colitis limited to the rectum only or to less than 20 cm of the colon Participants with stoma Participants with fistula or history of fistula Participants who require, or required within the 2 months prior to screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from study agent treatment Participants with symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Golimumab<br> | Drug: Golimumab<br>* Participants will receive 200 mg golimumab at Week 0 and 100 mg golimumab at Week 2 as a subcutaneous (SC) (under the skin) injection in the induction phase. Participants who have a clinical response in the induction phase and are randomly allocated to golimumab in the maintenance phase will receive 100 mg SC every 4 weeks through Week 52. Participants who do not have a clinical response in the induction phase will receive 100 mg of golimumab SC at Week 4 and will continue with 100 mg of golimumab SC every 4 weeks through Week 52 only if a response is obtained by Week 8.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Participants who have a clinical response to golimumab in the induction phase and are randomly allocated to placebo in the maintenance phase will receive SC placebo every 4 weeks through Week 52. However, participants receiving placebo and who will lose clinical response any time during the study will be eligible to receive 100 mg golimumab SC every 4 weeks through Week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Clinical Response Through Maintenance-Week 54 Measured Using the Mayo Score | Clinical response was defined as a decrease from Induction-Week 0 in the Mayo score by greater than or equal to (>=) 30 percent and >=3 points, with a decrease in the rectal bleeding subscore of >= 1 or a rectal bleeding subscore of 0 or 1. The Mayo score is the primary tool for assessing ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, findings of endoscopy, and physician's global assessment) which range from 0 to 3. The Mayo score is calculated as the sum of these 4 subscores and can range between 0 and 12. A score of 3 to 5 points indicates mildly active disease; a score of 6 to 10 indicates moderately active disease; and a score of 11 to 12 indicates severe disease. | Up to Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Clinical Remission at Both Maintenance-Week 30 and Week 54 | Clinical remission (as measured by the Mayo score) was defined as a Mayo score of less than or equal to (<=) 2 points, with no individual sub-score greater than (>) 1. | Weeks 30 and 54 | 
| Number of Participants With Mucosal Healing at Both Maintenance-Week 30 and Week 54 | Mucosal healing is defined as an endoscopy subscore of 0 or 1, where 0 indicates normal or inactive disease and 1 indicates mild disease (erythema, decreased vascular pattern, mild friability). Endoscopy subscore is one of the 4 subscores of the Mayo score. | Weeks 30 and 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, Japanese, Subcutaneous, Golimumab