Clinical trial NCT00094458: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn Disease
Keywords: Crohn's Disease
infliximab
azathioprine
Remicade
SONIC
Lead sponsor: Centocor Ortho Biotech Services, L.L.C.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2004-10-20
Enrollment: 508
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Participants With Corticosteriod-free Clinical Remission
timeFrame: Week 26
Secondary outcomes:
measure: Percentage of Participants With Mucosal Healing
timeFrame: Week 26
measure: Percentage of Participants With Corticosteroid-free Clinical Remission (Study Extension)
timeFrame: Week 50
measure: Percentage of Participants With Clinical Remission (Main Study)
timeFrame: Weeks 2, 6, 10, 18 and 26
measure: Percentage of Participants With Clinical Remission (Study Extension)
timeFrame: Weeks 34, 42 and 50
measure: Percentage of Participants With Clinical Response Over Time (Main Study)
timeFrame: Weeks 2, 6, 10, 18, 26
measure: Percentage of Participants With Clinical Response Over Time (Study Extension)
timeFrame: Weeks 34, 42, 50
measure: Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study)
timeFrame: Baseline and Weeks 2, 6, 10, 18, 26
measure: Average Corticosteroid Use
timeFrame: Weeks 2, 6, 10, 18 and 26
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Orange
country: United States
state: California
city: Roseville
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Golden
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Gainesville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: N Miami Beach
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Austell
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Peoria
country: United States
state: Illinois
city: Clive
country: United States
state: Iowa
city: Overland Park
country: United States
state: Kansas
city: Topeka
country: United States
state: Kansas
city: Baton Rouge
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: Troy
country: United States
state: Michigan
city: Plymouth
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Ocean Springs
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Urbana
country: United States
state: Missouri
city: Lincoln
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state: Nebraska
city: Egg Harbor Township
country: United States
state: New Jersey
city: Great Neck
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Bend
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Hatfield
country: United States
state: Pennsylvania
city: Lancaster
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Bellevue
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Hall In Tirol
country: Austria
city: Wien
country: Austria
city: Bonheiden
country: Belgium
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Roeselare
country: Belgium
city: Montreal
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Quebec
country: Canada
city: Aalborg
country: Denmark
city: Aarhus C.
country: Denmark
city: Helsinge
country: Denmark
city: Amiens Cedex 1
country: France
city: Bordeaux
country: France
city: Caen
country: France
city: Grenoble
country: France
city: Lille
country: France
city: Nancy
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Berlin
country: Germany
city: Frankfurt/Main
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Herne
country: Germany
city: Kiel
country: Germany
city: Magdeburg
country: Germany
city: Mainz
country: Germany
city: Minden
country: Germany
city: Munchen
country: Germany
city: Munster
country: Germany
city: Athens
country: Greece
city: Exohi
country: Greece
city: Heraklion- Crete
country: Greece
city: Nicea
country: Greece
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Petah Tikva
country: Israel
city: Tel-Aviv
country: Israel
city: Dordrecht
country: Netherlands
city: Eindhoven
country: Netherlands
city: Rotterdam
country: Netherlands
city: Oslo N/A
country: Norway
city: Oslo
country: Norway
city: Amadora
country: Portugal
city: Coimbra
country: Portugal
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Santander
country: Spain
city: Santiago De Compostela
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Stockhollm
country: Sweden
city: Stockholm
country: Sweden
city: Bristol
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Leeds
country: United Kingdom
city: Livingston
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Stockport
country: United Kingdom
Study officials:
affiliation: Centocor Ortho Biotech Services, L.L.C.
name: Centocor Ortho Biotech Services, L.L.C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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 disease. N Engl J Med. 2010 Apr 15;362(15):1383-95. doi: 10.1056/NEJMoa0904492.
citation: Dulai PS, Wong ECL, Reinisch W, Narula N. Clinical Decision Support Tool for Infliximab in Crohn's Disease. Clin Gastroenterol Hepatol. 2022 May;20(5):e1192-e1195. doi: 10.1016/j.cgh.2021.06.037. Epub 2021 Jun 30.
citation: Colombel JF, Adedokun OJ, Gasink C, Gao LL, Cornillie FJ, D'Haens GR, Rutgeerts PJ, Reinisch W, Sandborn WJ, Hanauer SB. Combination Therapy With Infliximab and Azathioprine Improves Infliximab Pharmacokinetic Features and Efficacy: A Post Hoc Analysis. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1525-1532.e1. doi: 10.1016/j.cgh.2018.09.033. Epub 2018 Sep 26.
citation: Colombel JF, Reinisch W, Mantzaris GJ, Kornbluth A, Rutgeerts P, Tang KL, Oortwijn A, Bevelander GS, Cornillie FJ, Sandborn WJ. Randomised clinical trial: deep remission in biologic and immunomodulator naive patients with Crohn's disease - a SONIC post hoc analysis. Aliment Pharmacol Ther. 2015 Apr;41(8):734-46. doi: 10.1111/apt.13139. Epub 2015 Mar 1.
citation: Reinisch W, Colombel JF, Sandborn WJ, Mantzaris GJ, Kornbluth A, Adedokun OJ, Miller M, Tang KL, Rutgeerts P, Cornillie F. Factors associated with short- and long-term outcomes of therapy for Crohn's disease. Clin Gastroenterol Hepatol. 2015 Mar;13(3):539-547.e2. doi: 10.1016/j.cgh.2014.09.031. Epub 2014 Sep 19.
citation: Peyrin-Biroulet L, Reinisch W, Colombel JF, Mantzaris GJ, Kornbluth A, Diamond R, Rutgeerts P, Tang LK, Cornillie FJ, Sandborn WJ. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's disease in the SONIC trial. Gut. 2014 Jan;63(1):88-95. doi: 10.1136/gutjnl-2013-304984. Epub 2013 Aug 23.
citation: Ferrante M, Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens GR, van der Woude CJ, Danese S, Diamond RH, Oortwijn AF, Tang KL, Miller M, Cornillie F, Rutgeerts PJ; International Organization for the Study of Inflammatory Bowel Diseases. Validation of endoscopic activity scores in patients with Crohn's disease based on a post hoc analysis of data from SONIC. Gastroenterology. 2013 Nov;145(5):978-986.e5. doi: 10.1053/j.gastro.2013.08.010. Epub 2013 Aug 14.