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

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Infliximab 5 mg/kg; Drug: Infliximab 10 mg/kg; Drug: Infliximab 20 mg/kg; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo will be adminstered at Week 0, 2 and 6.
Experimental: Infliximab 5 mg/kg	Drug: Infliximab 5 mg/kg; Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 10 milligram per kilogram (mg/kg) will be administered as infusion at Week 0, 2 and 6.; Other Names: anti-TNF chimeric monoclonal antibody (cA2)
Experimental: Infliximab 10 mg/kg	Drug: Infliximab 10 mg/kg; Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 5 mg/kg will be administered as infusion at Week 0, 2 and 6.; Other Names: anti-TNF chimeric monoclonal antibody (cA2)
Experimental: Infliximab 20 mg/kg	Drug: Infliximab 20 mg/kg; Infliximab (anti-TNF chimeric monoclonal antibody [cA2]) 20 mg/kg will be administered as infusion at Week 0, 2 and 6.; Other Names: anti-TNF chimeric monoclonal antibody (cA2)

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Centocor, Inc.

Publications and helpful links

General Publications

• Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med. 1997 Oct 9;337(15):1029-35. doi: 10.1056/NEJM199710093371502.

Study record dates

Study Major Dates

• Study Start: June 1, 1995
• Primary Completion (Actual): October 1, 1996
• Study Completion (Actual): October 1, 1996

Study Registration Dates

• First Submitted: December 22, 2005
• First Submitted That Met QC Criteria: December 22, 2005
• First Posted (Estimate): December 26, 2005

Study Record Updates

• Last Update Posted (Estimate): November 4, 2014
• Last Update Submitted That Met QC Criteria: November 3, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Crohn's Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Infliximab
• Other Study ID Numbers: CR006256