An Efficacy and Safety Study of Anti-TNF Monoclonal Antibody in Patients With Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and safety of anti-TNF chimeric monoclonal antibody (cA2) compared to placebo in patients with active Crohn's disease.

Detailed Description
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This is a randomized, placebo-controlled, double-blind, dose-ranging study followed by a placebo-controlled, double-blind, repeated-dose extension to evaluate the effectiveness and safety of anti-TNF chimeric monoclonal antibody (cA2) compared to placebo in the treatment of patients with active Crohn's disease. The primary efficacy outcome of the study is a comparison of the proportion of patients achieving a clinical response at the 4-week evaluation. Clinical response is defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of at least 70 points. Additional measurements of effectiveness include the clinical response over time, the time to loss of response, clinical remission over time, and changes in the Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Endoscopic Index of Severity (CDEIS) scores and C-reactive protein values. Anti-TNF Chimeric Monoclonal Antibody (cA2) or placebo

Official Title
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A Placebo-Controlled, Dose-Ranging Study Followed by a Placebo-Controlled, Repeated-Dose Extension of Anti-TNF Chimeric Monoclonal Antibody (cA2) in the Treatment of Patients With Active Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: Infliximab 5 mg/kg
* Drug: Infliximab 10 mg/kg
* Drug: Infliximab 20 mg/kg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Crohn's disease of at least 6 months duration, with colitis, ileitis, or ileocolitis confirmed by radiography or endoscopy Having a Crohn's Disease Activity Index (CDAI) of >=220 and <=400 Treated with at least 1 of the following: current use of oral corticosteroid therapy of <=40 mg/day (prednisone equivalent), current use of (or lack of response to) >=2 g/day of sulfasalazine (or equivalent) or >=800 mg of mesalamine, current use of (or lack of response to) azathioprine or 6-mercaptopurine, failure to respond to methotrexate or cyclosporine, (with a stop date at least 3 months prior to screening) If using oral corticosteroids, sulfasalazine or mesalamine, a start date at least 8 weeks prior to screening, with a stable dose of sulfasalazine or mesalamine for at least 4 weeks prior to screening and a stable dose of oral corticosteroids for at least 2 weeks prior to screening If not currently using oral corticosteroids, a stop date of any previous corticosteroid regimen of at least 4 weeks prior to screening and if not using sulfasalazine, mesalamine, azathioprine or 6-mercaptopurine, a stop date of any previous treatment with these agents of at least 8 weeks prior to screening Exclusion Criteria: Patients with Crohn's disease limited to the stomach or proximal small intestine Having symptomatic stenosis or ileal strictures that might have require surgical intervention or that might render patients unresponsive to cA2 treatment Who have received treatment with parenteral corticosteroid or adrenocorticotrophic hormone within 4 weeks prior to screening, or currently requiring oral or parenteral corticosteroid therapy for another disease such as asthma Having a serious infection, such as hepatitis, pneumonia or pyelonephritis in the 3 months prior to screening, a history of opportunistic infection such as herpes zoster within 2 months prior to screening, or evidence of active cytomegalovirus, active pneumocystis carinii, or drug resistant atypical mycobacterium Having active signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease, or any current known malignancy or any history of malignancy which would put the patient at an unacceptable risk for participation in the study or that would be expected to limit life expectancy

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 |
| --- | --- |
| Experimental: Infliximab 5 mg/kg<br> | Drug: Infliximab 5 mg/kg<br>* Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 10 milligram per kilogram (mg/kg) will be administered as infusion at Week 0, 2 and 6.<br>* Other names: anti-TNF chimeric monoclonal antibody (cA2);|
| Experimental: Infliximab 10 mg/kg<br> | Drug: Infliximab 10 mg/kg<br>* Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 5 mg/kg will be administered as infusion at Week 0, 2 and 6.<br>* Other names: anti-TNF chimeric monoclonal antibody (cA2);|
| Experimental: Infliximab 20 mg/kg<br> | Drug: Infliximab 20 mg/kg<br>* Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 20 mg/kg will be administered as infusion at Week 0, 2 and 6.<br>* Other names: anti-TNF chimeric monoclonal antibody (cA2);|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo will be adminstered at Week 0, 2 and 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the proportion of patients achieving a clinical response at Week 4 | Clinical response is defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of at least 70 points. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response over time; Time to loss of response; Clinical remission over time; Changes in CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ) and Crohn's Disease Endoscopic Index of Severity (CDEIS) scores and C-reactive protein values |  | up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease