A Study of the Safety and Efficacy of Infliximab(REMICADE ) in Pediatric Patients With Moderately to SeverelyActive Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effectiveness and safety of infliximab (Remicade) in children with moderately to severely active ulcerative colitis.

Detailed Description
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Ulcerative Colitis (UC) is a disorder involving the lining of the colon. A substance called tumor necrosis factor (TNF) naturally occurs in the body. TNF is thought to play an important role in the development of ulcerative colitis by causing some of the damage that is seen in the colon. Antibodies are normally made in the body and help fight off infection. Infliximab is an antibody that is made in a scientific laboratory, using parts of both mouse and human antibodies. It has been designed to attach to TNF, making it difficult for TNF to do any damage. This study will be done at centers in North America and Europe. Each child will first have a clinic visit (screening visit) to have some tests done to make sure the child is the type of patient who should be in this study. At the 2nd visit (week 0), the child will have the first treatment with infliximab. All children in the study will receive 5 mg/kg infliximab 3 times (at weeks 0, 2 and 6) over the first 6 weeks of the study. If the child's symptoms do not improve by the 8th week, the child will receive no further infusions, but will return for safety evaluations. If the child's symptoms do improve, the child will be randomly assigned (like the flip of a coin) to either 5 mg/kg infliximab every 8 weeks through week 46 or 5 mg/kg infliximab every 12 weeks through week 42. If the child gets worse after being randomly assigned, the amount of infliximab may be increased or the infliximab may be given more frequently. A final infusion will be given at either week 42 or week 46. There will be a safety evaluation at week 54 and a visit at week 62 to get a blood sample. Patients will receive 5 mg/kg of infliximab at weeks 0, 2 and 6 and then 5mg/kg infliximab either every 8 weeks or 12 weeks until weeks 42 or 46. Infliximab is given as an intravenous infusion over 2 hours.

Official Title
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A Phase 3, Randomized, Open-label, Parallel-group, Multicenter Trial to Evaluate the Safety and Efficacy of Infliximab (REMICADE�) in Pediatric Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Biological: infliximab
* Biological: infliximab
* Biological: infliximab
* Biological: infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have moderately to severely active ulcerative colitis Diagnosed with ulcerative colitis for 2 weeks before screening Male patients who are sexually active and female patients who are sexually active or of childbearing potential must use adequate birth control while participation in the study and for 6 months after the last infusion. Exclusion Criteria: History of latent or active TB Have had a live viral or bacterial vaccination within 3 months before screening Have or have had serious infections within 3 months before screening Prior treatment with infliximab

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 002<br>infliximab infusion of 5mg/kg at weeks 0, 2, 6 followed by every 12 wks through week 42; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 42; infliximab - Could receive infusion of 5mg/kg every 8 weeks up to week 42 | Biological: infliximab<br>* infusion of 5mg/kg at weeks 0, 2, 6 followed by every 12 wks through week 42; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 42; infliximab - Could receive infusion of 5mg/kg every 8 weeks up to week 42<br>Biological: infliximab<br>* infliximab - Could receive infusion of 10 mg/kg every 8 weeks up to week 42<br>|
| Experimental: 001<br>infliximab infusion of 5mg/kg at weeks 0, 2, 6 followed by every 8 wks through week 46; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 46 | Biological: infliximab<br>* infusion of 5mg/kg at weeks 0, 2, 6 followed by every 8 wks through week 46; infliximab - Could receive infusion of 10mg/kg every 8 weeks up to week 46<br>Biological: infliximab<br>* infusion of 5mg/kg at weeks 0, 2, 6, then every 12 wks through week 42<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Clinical Response at Week 8 | Range is 0 to 12 points, where 0 is the least disease activity, and 12 is the most disease activity. Clinical response at Week 8 is defined as a decrease from baseline in the Mayo score(based on symptoms of ulcerative colitis) by >=30% and >= 3 points, with a decrease in the rectal bleeding subscore >=1 or a rectal bleeding subscore of 0 or 1. Treatment failure rules (patients who discontinued study agent due to lack of therapeutic effect, had a colectomy or ostomy, or had protocol-prohibited medication changes) were applied to determine the final clinical response status for each patient. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Pediatric Ulcerative Colitis Activity Index (PUCAI) Remission at Week 54 | Range is 0 to 85 points, where 0 is the least disease activity, and 85 is the most disease activity. Remission is a score <10. In addition to the PUCAI remission status, treatment failure rules (patients who discontinued study agent due to lack of therapeutic effect, had a colectomy or ostomy, had protocol-prohibited medication changes, or stepped up) were applied to determine the final PUCAI. | Week 54 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative colitis, inflammatory bowel disease, children