COMMIT (Combination Of Maintenance Methotrexate-Infliximab Trial)

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
University of Western Ontario, Canada
ClinicalTrials.gov Identifier:
NCT00132899
First received: August 19, 2005
Last updated: December 10, 2013
Last verified: December 2005
  Purpose

The primary objective is to compare the efficacy and safety of infliximab plus methotrexate to infliximab alone for the long-term control of signs and symptoms of Crohn's disease (CD) in patients with symptoms that are persistent enough to require corticosteroid therapy.


Condition Intervention Phase
Crohn's Disease
Drug: Methotrexate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Multi-Centre Study to Evaluate the Safety and Efficacy of Infliximab in Combination With Methotrexate for the Long-term Treatment of Crohn's Disease (CD)

Resource links provided by NLM:


Further study details as provided by University of Western Ontario, Canada:

Primary Outcome Measures:
  • Treatment success as defined by the proportion of subjects in clinical remission (i.e. complete discontinuation of prednisone therapy and a CDAI score of <150) at week 14, and maintenance of clinical remission between study weeks 14 and 50 [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy of infliximab therapy in combination with methotrexate on disease activity using the Crohn's Disease Activity Index (CDAI) and Investigator and Subject Global Ratings [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Effects of infliximab therapy in combination with methotrexate on health-related quality of life [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Proportion of subjects who develop antibodies to infliximab [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 128
Study Start Date: December 2005
Study Completion Date: July 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Methotrexate
Methotrexate and infliximab combination
Drug: Methotrexate
Methotrexate and infliximab combination
Placebo Comparator: Placebo
Placebo plus infliximab combination
Drug: Placebo
Placebo and infliximab combination therapy.

Detailed Description:

The current approach to the treatment of Crohn's Disease is based on "step care". This strategy is relatively ineffective for the long-term management of patients who require treatment with corticosteroids. Although azathioprine, methotrexate and infliximab are modestly effective in this high-risk population, long-term corticosteroid-free response rates are low. Thus combination therapy is an attractive option to explore. Based on a favourable experience with dual therapy in the treatment of rheumatoid arthritis and the demonstrated efficacy of methotrexate in corticosteroid-dependent CD, we expect that combination therapy with methotrexate and infliximab will be significantly more effective than infliximab monotherapy. Furthermore combined therapy is likely to be highly effective in preventing formation of the antibodies to infliximab that are an important limitation to the continued successful use of this drug.

This is a randomized, placebo-controlled, double-blind, parallel group, multi-centre study. Subjects who have initiated corticosteroid induction therapy within the preceding 6 weeks will be randomized (irrespective of CDAI defined disease activity) in a 1:1 ratio to either methotrexate or placebo for a period of 50 weeks in combination with infliximab administered for 8 infusions. Randomization will be stratified by:

  • Treatment with or without Imuran/6-mercaptopurine in the 2-12 months prior to randomization;
  • Prednisone dose <20 mg or ≥20 mg daily at randomization;
  • CDAI <150 or ≥150 at randomization.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male, or non-pregnant/non-lactating females, 18 or older
  • Established Crohn's disease with active symptoms requiring prednisone therapy.
  • Females of child-bearing potential must have a negative pregnancy test and must agree to use adequate contraception

Exclusion Criteria:

  • Intolerance or hypersensitivity to infliximab, methotrexate, prednisone and or known allergy to murine proteins or other chimeric proteins
  • Are pregnant, nursing, or planning pregnancy (both men and women) during or in the 6 months after the study
  • In the 2 months prior to screening, have had a serious infection, or have been hospitalized for and/or treated with intravenous (IV) antibiotics for infection. In the 6 months prior to screening, have had an opportunistic infection.
  • After screening, need to continue non-study medical therapy for CD
  • In the 8 weeks prior to screening, have received any of the following: systemic steroid therapy, azathioprine, 6-mercaptopurine, cyclosporine, probiotic products, or omega-3 fatty acids
  • Have received any of the following: biologics in the last 6 months; methotrexate in the last year; and/or ever received infliximab.
  • Have any of the following: biopsy-proven cirrhosis, clinically important lung disease, pre-existing demyelinating disorder, systemic lupus erythematosus, congestive heart failure, diabetes mellitus (insulin dependent), increased risk for steroid-related side effects, body weight 40% higher than standard, human immunodeficiency virus and/or hepatitis B or hepatitis C
  • Have any of the following: an active draining fistula as the primary manifestation of CD; documented short bowel syndrome; a stoma; or severe, and/or fixed symptomatic stenosis of the intestine.
  • Have had any of the following: clinically important bowel obstruction in the last 3 months; a bowel resection in the last 3 months; and/or other intra-abdominal surgery within 6 months.
  • Clinically significant impairment in cardiac, liver or renal function; central nervous system (CNS), pulmonary, hematological, immunological, vascular and gastrointestinal disease in addition to CD; current malignancy or malignancy within 5 years prior to screening.
  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: NCT00132899

Locations
Canada, Ontario
Robarts Clinical Trials, Robarts Research Institute
London, Ontario, Canada, N6A 5K8
Sponsors and Collaborators
University of Western Ontario, Canada
Schering-Plough
Investigators
Study Director: Brian G Feagan, MD, M.Sc Robarts Clinical Trials, Robarts Research Institute
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Western Ontario, Canada
ClinicalTrials.gov Identifier: NCT00132899     History of Changes
Other Study ID Numbers: RP0401
Study First Received: August 19, 2005
Last Updated: December 10, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of Western Ontario, Canada:
Crohn's Disease
multi-centre randomized placebo-controlled
infliximab
methotrexate
inflammatory bowel disease

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Methotrexate
Infliximab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Gastrointestinal Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 20, 2014