Trial Comparing Infliximab and Infliximab and Azathioprine in the Treatment of Patients With Crohn's Disease na�ve to Both Immunomodulators and Biologic Therapy (Study of Biologic and Immunomodulator Naive Patients in Chrohn's Disease: SONIC

Crohn Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094458
• Other study ID #: CR004804
• Secondary ID: C0168T67
• Status: Completed
• Phase: Phase 3
• First received: October 19, 2004
• Last updated: April 2, 2014
• Start date: March 2005
• Est. completion date: December 2009

Study information

• Verified date: April 2014
• Source: Centocor Ortho Biotech Services, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and effectiveness of three different treatments for patients with Crohns 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.

Description:

Crohns disease is characterized by inflammation (the changes that happen when tissues in the body are injured) and ulceration (open sores) of the intestines. Crohns disease is treated with medications that decrease inflammation, and reduce diarrhea, abdominal pain and other symptoms of Crohns disease. In addition, Crohns 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 Crohns disease. Infliximab is currently approved by the FDA for the treatment of both Crohns disease and rheumatoid arthritis. Azathioprine, which is an investigational drug, has not been approved by the FDA for the treatment of Crohns disease, but it is a well-established therapy that has been used for many years to treat Crohns disease. This study seeks to determine whether infliximab, azathioprine, or the combination of both drugs would be the most appropriate treatment for Crohns 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 Crohns 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 508
• Est. completion date: December 2009
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of Crohns 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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease

Intervention

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

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Centocor Ortho Biotech Services, L.L.C.	Schering-Plough

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Greece,  Israel,  Netherlands,  Norway,  Portugal,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's dise — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical Remission	Clinical remission is defined as a CDAI < 150	Week 52 of Open Label Extension	No
Primary	Corticosteriod-free Clinical Remission	Corticosteroid-free clinical remission is defined as a Crohn's Disease Activity Index (CDAI) < 150 in subjects who have not received any dose of systemic corticosteroids (prednisone or equivalent) for >= 3 weeks and have not received budesonide at a dose > 6mg/day for >= 3 weeks. The total CDAI score ranges from 0 - 600. The lower the CDAI score, the better (i.e., 0 is better and 600 is worse).	Week 26	No
Secondary	Mucosal Healing	Complete absence of mucosal ulcerations in the colon and terminal ileum as assessed by video endoscopy	Week 26	No
Secondary	Corticosteroid-free Clinical Remission	Corticosteroid-free clinical remission is defined as a Crohn's Disease Activity Index (CDAI) < 150 who have not received any dose of systemic corticosteroids (prednisone or equivalent) for >= 3 weeks and have not received budesonide at a dose > 6mg/day for >= 3 weeks	Week 50	No
Secondary	Clinical Remission Over Time	Clinical remission is defined as a CDAI < 150, compared to baseline (Week 0)	Weeks 26 and 50 (Remission was also measured at Weeks 2, 6, 10, 18, 34 and 42)	No
Secondary	Clinical Response Over Time	Clinical response is defined as >= 100 point decrease in CDAI, compared to baseline (Week 0).	Weeks 26 and 50 (Response was also measured at Weeks 2, 6, 10, 18, 34 and 42)	No
Secondary	Quality of Life	Quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ). The IBDQ is a 32-item questionnaire and the total IBDQ score can range from 32 (very poor) to 224 (perfect).	Weeks 26 and 50 (Quality of Life was also assessed at Weeks 0, 2, 6, 10, 18, 34 and 42)	No
Secondary	Average Corticosteroid Use	Average daily dose of systemic corticosteroid concomitant medications(prednisone or equivalent)	Weeks 26 and 50 (Corticosteroid use was also measured at Weeks 0, 2, 6, 10, 18, 34 and 42)	No