- ICH GCP
- US Clinical Trials Registry
- 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
December 15, 2016 updated by: Centocor Ortho Biotech Services, L.L.C.
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 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.
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
508
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Hall In Tirol, Austria
-
Wien, Austria
-
-
-
-
-
Bonheiden, Belgium
-
Bruxelles, Belgium
-
Leuven, Belgium
-
Liege, Belgium
-
Roeselare, Belgium
-
-
-
-
-
Quebec, Canada
-
-
Ontario
-
Montreal, Ontario, Canada
-
Toronto, Ontario, Canada
-
-
-
-
-
Aalborg, Denmark
-
Aarhus C., Denmark
-
Helsinge, Denmark
-
-
-
-
-
Amiens Cedex 1, France
-
Bordeaux, France
-
Caen, France
-
Grenoble, France
-
Lille, France
-
Nancy, France
-
Paris, France
-
Toulouse, France
-
-
-
-
-
Berlin, Germany
-
Frankfurt/Main, Germany
-
Hamburg, Germany
-
Hannover, Germany
-
Herne, Germany
-
Kiel, Germany
-
Magdeburg, Germany
-
Mainz, Germany
-
Minden, Germany
-
Munchen, Germany
-
Munster, Germany
-
-
-
-
-
Athens, Greece
-
Exohi, Greece
-
Heraklion- Crete, Greece
-
Nicea, Greece
-
-
-
-
-
Haifa, Israel
-
Jerusalem, Israel
-
Kfar Saba, Israel
-
Petah Tikva, Israel
-
Tel-Aviv, Israel
-
-
-
-
-
Dordrecht, Netherlands
-
Eindhoven, Netherlands
-
Rotterdam, Netherlands
-
-
-
-
-
Oslo, Norway
-
Oslo N/A, Norway
-
-
-
-
-
Amadora, Portugal
-
Coimbra, Portugal
-
-
-
-
-
Barcelona, Spain
-
Madrid, Spain
-
Santander, Spain
-
Santiago De Compostela, Spain
-
Sevilla, Spain
-
Valencia, Spain
-
-
-
-
-
Linköping, Sweden
-
Lund, Sweden
-
Stockhollm, Sweden
-
Stockholm, Sweden
-
-
-
-
-
Bristol, United Kingdom
-
Cambridge, United Kingdom
-
Leeds, United Kingdom
-
Livingston, United Kingdom
-
London, United Kingdom
-
Newcastle Upon Tyne, United Kingdom
-
Stockport, United Kingdom
-
-
-
-
Alabama
-
Birmingham, Alabama, United States
-
-
Arizona
-
Phoenix, Arizona, United States
-
-
California
-
Orange, California, United States
-
Roseville, California, United States
-
San Diego, California, United States
-
San Luis Obispo, California, United States
-
-
Colorado
-
Golden, Colorado, United States
-
Littleton, Colorado, United States
-
-
Connecticut
-
Hartford, Connecticut, United States
-
-
Florida
-
Gainesville, Florida, United States
-
Jacksonville, Florida, United States
-
N Miami Beach, Florida, United States
-
Winter Park, Florida, United States
-
-
Georgia
-
Austell, Georgia, United States
-
Decatur, Georgia, United States
-
Savannah, Georgia, United States
-
-
Illinois
-
Peoria, Illinois, United States
-
-
Iowa
-
Clive, Iowa, United States
-
-
Kansas
-
Overland Park, Kansas, United States
-
Topeka, Kansas, United States
-
-
Louisiana
-
Baton Rouge, Louisiana, United States
-
Metairie, Louisiana, United States
-
-
Michigan
-
Troy, Michigan, United States
-
-
Minnesota
-
Plymouth, Minnesota, United States
-
Rochester, Minnesota, United States
-
-
Mississippi
-
Ocean Springs, Mississippi, United States
-
Tupelo, Mississippi, United States
-
-
Missouri
-
Saint Louis, Missouri, United States
-
Urbana, Missouri, United States
-
-
Nebraska
-
Lincoln, Nebraska, United States
-
-
New Jersey
-
Egg Harbor Township, New Jersey, United States
-
-
New York
-
Great Neck, New York, United States
-
New Hyde Park, New York, United States
-
New York, New York, United States
-
-
North Carolina
-
Asheville, North Carolina, United States
-
Charlotte, North Carolina, United States
-
Raleigh, North Carolina, United States
-
Wilmington, North Carolina, United States
-
-
Oregon
-
Bend, Oregon, United States
-
Portland, Oregon, United States
-
-
Pennsylvania
-
Hatfield, Pennsylvania, United States
-
Lancaster, Pennsylvania, United States
-
Philadelphia, Pennsylvania, United States
-
Pittsburgh, Pennsylvania, United States
-
-
South Carolina
-
Columbia, South Carolina, United States
-
-
Texas
-
Austin, Texas, United States
-
Houston, Texas, United States
-
San Antonio, Texas, United States
-
-
Washington
-
Bellevue, Washington, United States
-
Spokane, Washington, United States
-
Tacoma, Washington, United States
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 99 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 003
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
|
AZA daily 2.5 mg/kg/day and IFX infusions 5 mg/kg at weeks 0, 2, 6, 14, and 22
|
EXPERIMENTAL: 001
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
|
AZA daily 2.5 mg/kg/day and placebo IFX infusions at weeks 0, 2, 6, 14, and 22
|
EXPERIMENTAL: 002
infliximab infusion; AZA placebo caps Infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22 and placebo AZA capsules
|
Infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22 and placebo AZA capsules
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Corticosteriod-free Clinical Remission
Time Frame: Week 26
|
Corticosteroid-free clinical remission is defined as a Crohn's Disease Activity Index (CDAI) less than (<) 150 in participants who have not received any dose of systemic corticosteroids (prednisone or equivalent) for greater than or equal to (>=) 3 weeks and have not received budesonide at a dose > 6 milligram per day (mg/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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Mucosal Healing
Time Frame: Week 26
|
Complete absence of mucosal ulcerations in the colon and terminal ileum as assessed by video endoscopy.
|
Week 26
|
Percentage of Participants With Corticosteroid-free Clinical Remission (Study Extension)
Time Frame: Week 50
|
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 > 6 milligram per day (mg/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 50
|
Percentage of Participants With Clinical Remission (Main Study)
Time Frame: Weeks 2, 6, 10, 18 and 26
|
Clinical remission is defined as a CDAI < 150, compared to baseline (Week 0)
|
Weeks 2, 6, 10, 18 and 26
|
Percentage of Participants With Clinical Remission (Study Extension)
Time Frame: Weeks 34, 42 and 50
|
Clinical remission is defined as a CDAI < 150, compared to baseline (Week 0)
|
Weeks 34, 42 and 50
|
Percentage of Participants With Clinical Response Over Time (Main Study)
Time Frame: Weeks 2, 6, 10, 18, 26
|
Clinical response, defined as a >=100-point decrease in CDAI from Baseline.
|
Weeks 2, 6, 10, 18, 26
|
Percentage of Participants With Clinical Response Over Time (Study Extension)
Time Frame: Weeks 34, 42, 50
|
Clinical response, defined as a >=100-point decrease in CDAI from Baseline.
|
Weeks 34, 42, 50
|
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score at Weeks 2, 6, 10, 18 and 26 (Main Study)
Time Frame: Baseline and Weeks 2, 6, 10, 18, 26
|
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).
|
Baseline and Weeks 2, 6, 10, 18, 26
|
Average Corticosteroid Use
Time Frame: Weeks 2, 6, 10, 18 and 26
|
Average daily dose of systemic corticosteroid concomitant medications(prednisone or equivalent)
|
Weeks 2, 6, 10, 18 and 26
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2005
Primary Completion (ACTUAL)
April 1, 2008
Study Completion (ACTUAL)
December 1, 2009
Study Registration Dates
First Submitted
October 19, 2004
First Submitted That Met QC Criteria
October 19, 2004
First Posted (ESTIMATE)
October 20, 2004
Study Record Updates
Last Update Posted (ESTIMATE)
February 9, 2017
Last Update Submitted That Met QC Criteria
December 15, 2016
Last Verified
December 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Gastrointestinal Diseases
- Gastroenteritis
- Intestinal Diseases
- Inflammatory Bowel Diseases
- Crohn Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Dermatologic Agents
- Infliximab
- Azathioprine
Other Study ID Numbers
- CR004804
- C0168T67
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Crohn Disease
-
ProgenaBiomeRecruitingCrohn Disease | Crohn Colitis | Crohn's Ileocolitis | Crohn's Gastritis | Crohn's Jejunitis | Crohn's Duodenitis | Crohn's Esophagitis | Crohn's | Crohn Disease of Ileum | Crohn Ileitis | Crohn's Disease Relapse | Crohns Disease Aggravated | Crohn Disease in Remission | Crohn's Disease of PylorusUnited States
-
Chinese University of Hong KongTerminatedCrohn Disease | Perianal Crohn DiseaseHong Kong
-
SandozCompletedCrohn´s DiseaseAustria, Germany, Poland, Spain, Sweden
-
Dr. Falk Pharma GmbHCompleted
-
University of Erlangen-Nürnberg Medical SchoolCompleted
-
Academisch Medisch Centrum - Universiteit van Amsterdam...CelltrionRecruitingBowel Disease | Inflammatory Disease | Disease CrohnNetherlands
-
Ferring PharmaceuticalsTerminatedCrohn´s DiseaseUnited Kingdom, United States, Germany, Belgium, Denmark, France, Sweden
-
Groupe Hospitalier Paris Saint JosephCompleted
-
Jinling Hospital, ChinaCompletedCrohn Disease in RemissionChina
-
Boehringer IngelheimTerminatedFibrostenotic Crohn´s DiseaseUnited States, Canada, Japan, Sweden
Clinical Trials on infliximab (IFX) infusion; azathioprine (AZA) caps
-
Merck Sharp & Dohme LLCTerminated
-
Children's Memorial Health Institute, PolandUnknown
-
Sixth Affiliated Hospital, Sun Yat-sen UniversityNot yet recruitingInflammatory Bowel Diseases | Crohn Disease | Polyunsaturated Acid Lipidosis
-
Children's Hospital of Fudan UniversityRecruitingCrohn Disease | Immunosuppression | Children, Only | InfliximabChina
-
Merck Sharp & Dohme LLCTerminated
-
Merck Sharp & Dohme LLCTerminated