COMMIT (Combination Of Maintenance Methotrexate-Infliximab Trial)

December 10, 2013 updated by: University of Western Ontario, Canada

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

128

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

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5K8
        • Robarts Clinical Trials, Robarts Research Institute

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
one year

Secondary Outcome Measures

Outcome Measure
Time Frame
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
one year
Effects of infliximab therapy in combination with methotrexate on health-related quality of life
Time Frame: one year
one year
Proportion of subjects who develop antibodies to infliximab
Time Frame: one year
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Western Ontario, Canada

Collaborators

Schering-Plough

Investigators

  • Study Director: Brian G Feagan, MD, M.Sc, Robarts Clinical Trials, Robarts Research Institute

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

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

December 1, 2005

Primary Completion (ACTUAL)

February 1, 2008

Study Completion (ACTUAL)

July 1, 2008

Study Registration Dates

First Submitted

August 19, 2005

First Submitted That Met QC Criteria

August 19, 2005

First Posted (ESTIMATE)

August 22, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

December 11, 2013

Last Update Submitted That Met QC Criteria

December 10, 2013

Last Verified

December 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RP0401

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's Disease

Clinical Trials on Methotrexate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Algeria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe