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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

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Centocor Ortho Biotech Services, L.L.C.
ClinicalTrials.gov Identifier:
NCT00094458
First received: October 19, 2004
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Crohn Disease
Biological: infliximab infusion; AZA placebo caps
Other: infliximab (IFX) infusion; azathioprine (AZA) caps
Drug: infliximab (IFX) placebo infusion; azathioprine (AZA) caps
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Centocor Ortho Biotech Services, L.L.C.:

Primary Outcome Measures:
  • Corticosteriod-free Clinical Remission [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Mucosal Healing [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    Complete absence of mucosal ulcerations in the colon and terminal ileum as assessed by video endoscopy

  • Corticosteroid-free Clinical Remission [ Time Frame: Week 50 ] [ Designated as safety issue: No ]
    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

  • Clinical Remission Over Time [ Time Frame: Weeks 26 and 50 (Remission was also measured at Weeks 2, 6, 10, 18, 34 and 42) ] [ Designated as safety issue: No ]
    Clinical remission is defined as a CDAI < 150, compared to baseline (Week 0)

  • Clinical Response Over Time [ Time Frame: Weeks 26 and 50 (Response was also measured at Weeks 2, 6, 10, 18, 34 and 42) ] [ Designated as safety issue: No ]
    Clinical response is defined as >= 100 point decrease in CDAI, compared to baseline (Week 0).

  • 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) ] [ Designated as safety issue: No ]
    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).

  • Average Corticosteroid Use [ Time Frame: Weeks 26 and 50 (Corticosteroid use was also measured at Weeks 0, 2, 6, 10, 18, 34 and 42) ] [ Designated as safety issue: No ]
    Average daily dose of systemic corticosteroid concomitant medications(prednisone or equivalent)


Other Outcome Measures:
  • Clinical Remission [ Time Frame: Week 52 of Open Label Extension ] [ Designated as safety issue: No ]
    Clinical remission is defined as a CDAI < 150


Enrollment: 508
Study Start Date: March 2005
Study Completion Date: December 2009
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
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
Experimental: 002
infliximab infusion; AZA placebo caps Infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22 and placebo AZA capsules
Biological: infliximab infusion; AZA placebo caps
Infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22 and placebo AZA capsules

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00094458

  Show 116 Study Locations
Sponsors and Collaborators
Centocor Ortho Biotech Services, L.L.C.
Schering-Plough
Investigators
Study Director: Centocor Ortho Biotech Services, L.L.C. Clinical Trial Centocor Ortho Biotech Services, L.L.C.
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centocor Ortho Biotech Services, L.L.C.
ClinicalTrials.gov Identifier: NCT00094458     History of Changes
Other Study ID Numbers: CR004804, C0168T67
Study First Received: October 19, 2004
Results First Received: April 30, 2009
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Centocor Ortho Biotech Services, L.L.C.:
Crohn's Disease
infliximab
azathioprine
Remicade
SONIC

Additional relevant MeSH terms:
Crohn Disease
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Adjuvants, Immunologic
Antibodies, Monoclonal
Azathioprine
Infliximab
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Central Nervous System Agents
Dermatologic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014