Official Title: “Multicenter, Randomized, Double-Blind, Active Controlled Trial Comparing REMICADE® (Infliximab) and REMICADE Plus Azathioprine to Azathioprine in the Treatment of Patients With Crohn's Disease Naive to Both Immunomodulators and Biologic Therapy”

The purpose of this study is to assess the safety and effectiveness of three different treatments for patients with Crohn's disease who have not responded to previous treatment with a group of drugs commonly used to treat Crohn's Disease (5-ASA) and corticosteroids.

Patients will receive either infliximab (a drug used to treat autoimmune diseases) or azathioprine (an immunosuppressant or drug used to suppress the immune system) or a combination of both for up to 34 weeks. This research study will involve approximately 500 patients. The main study involves up to 34 weeks (approximately 8 months). A study extension of an additional 20 weeks (approximately 5 months) is optional for patients who successfully complete the main study. A country-specific study extension of open label infliximab treatment for an additional 1 year is optional for patients who successfully complete the main study extension.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2008

Crohn's disease is characterized by inflammation (the changes that happen when tissues in the body are injured) and ulceration (open sores) of the intestines. Crohn's disease is treated with medications that decrease inflammation, and reduce diarrhea, abdominal pain and other symptoms of Crohn's disease. In addition, Crohn's disease can be treated with medications that suppress the immune system (the body system involved in inflammation and infections) or with surgery. This study will investigate the effectiveness of infliximab and azathioprine in the treatment of patients with moderate-to-severe Crohn's disease. Infliximab is currently approved by the FDA for the treatment of both Crohn's disease and rheumatoid arthritis.

Azathioprine, which is an investigational drug, has not been approved by the FDA for the treatment of Crohn's disease, but it is a well-established therapy that has been used for many years to treat Crohn's disease. This study seeks to determine whether infliximab, azathioprine, or the combination of both drugs would be the most appropriate treatment for Crohn's disease patients who have not responded well to certain drugs called 5-ASA drugs (e.g.

Asacol, Pentasa, sulfasalazine) and/or require frequent treatment with corticosteroids. This research study will involve approximately 500 patients.

Patients may participate in the main study for up to 34 weeks (approximately 8 months).

During the main study, patients will be asked to visit the study center for 10 visits. If patients enroll into the extension of the study, the total time for participation may be up to 54 weeks (approximately 13 months). Patients enrolled in the Study Extension will be asked to visit the study center for an additional 5 visits. A country-specific (EU and Israel only), prospective, multi-center, open-label extension of the study will further evaluate the long-term safety and efficacy of scheduled maintenance therapy with infliximab in patients with Crohn's Disease. Patients who have completed treatment through Week 50 in the SONIC main study and who, in the opinion of the investigator, would benefit from infliximab treatment may enter the open-label extension.

Patients will be randomly assigned to one of three treatment groups (either infliximab plus placebo capsules, infliximab plus azathioprine, or azathioprine plus placebo infusions - there is no possibility of being assigned to placebo only in this trial - patients will receive one or both of these medications) at the beginning of the study. Oral medication will be taken daily. There are 5 infusion (which will be either infliximab or placebo) visits during the main study.

Intervention(s) in this Clinical Trial

• Drug: infliximab (IFX) placebo infusion; azathioprine (AZA) caps
  • AZA daily 2.5 mg/kg/day and placebo IFX infusions at weeks 0, 2, 6, 14, and 22
• Biological: infliximab infusion; AZA placebo caps
  • Infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22 and placebo AZA capsules
• Other: infliximab (IFX) infusion; azathioprine (AZA) caps
  • AZA daily 2.5 mg/kg/day and IFX infusions 5 mg/kg at weeks 0, 2, 6, 14, and 22

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 001
• Experimental: 002
• Experimental: 003

Primary Measures

• Corticosteriod-Free Clinical Remission
  • Time Frame: Week 26
    Safety Issue?: No

Secondary Measures

• Mucosal Healing
  • Time Frame: Week 26
    Safety Issue?: No
• Corticosteroid-Free Clinical Remission
  • Time Frame: Week 50
    Safety Issue?: No
• Clinical Remission Over Time
  • Time Frame: Weeks 26 and 50 (Remission was also measured at Weeks 2, 6, 10, 18, 34 and 42)
    Safety Issue?: No
• Clinical Response Over Time
  • Time Frame: Weeks 26 and 50 (Response was also measured at Weeks 2, 6, 10, 18, 34 and 42)
    Safety Issue?: No
• Quality of Life
  • Time Frame: Weeks 26 and 50 (Quality of Life was also assessed at Weeks 0, 2, 6, 10, 18, 34 and 42)
    Safety Issue?: No
• Average Corticosteroid Use
  • Time Frame: Weeks 26 and 50 (Corticosteroid use was also measured at Weeks 0, 2, 6, 10, 18, 34 and 42)
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of Crohn's Disease for at least 6 weeks
• Moderate to severe disease activity (CDAI >= 220 and <=450)
• No history of azathioprine, 6-MP (6 Mercaptopurine), or biologic treatments
• Are either: Corticosteriod-dependent, OR considered for a 2nd (or greater) course of corticosteriod, OR 5-ASA failures, Or Budesonide failures

Exclusion Criteria:

• History of abdominal surgery within the last 6 months
• Have an ostomy or stoma [An operation to create an opening from an area inside the body to the outside]
• Are pregnant, nursing, or planning pregnancy (both men and women)
• Serious simultaneous illness that could interfere with study participation
• Use of any investigational drug within 30 days
• Have a concomitant diagnosis or any history of congestive heart failure
• Weigh more than 140 kilograms (or 310 pounds)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Centocor, Inc.

Overall Clinical Trial Officials and Contacts

Centocor, Inc. Clinical Trial Study Director Centocor, Inc.  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00094458

Study ID Number: CR004804

ClinicalTrials.gov Identifier: NCT00094458

Health Authority: United States: Food and Drug Administration