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 in patients with symptoms that are persistent enough to require corticosteroid therapy.

Condition	Intervention	Phase
Crohn''''s Disease	Drug: Infliximab - Methotrexate Combination Therapy	Phase III

Further Study Details: 

Primary Outcomes: 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.
Secondary Outcomes: Efficacy of infliximab therapy in combination with methotrexate on disease activity using the Crohn’s disease Activity Index (CDAI) Investigator and Subject Global Ratings; Effects of infliximab therapy in combination with methotrexate on health-related quality of life; Proportion of subjects who develop antibodies to infliximab; Safety and tolerability of infliximab therapy in combination with methotrexate
Expected Total Enrollment:  124

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 (1) Treatment with or without Imuran/6-mercaptopurine in the 2-12 months prior to randomization (2) Prednisone dose <20 mg or ≥20 mg daily at randomization (3) CDAI <150 or ≥150 at randomization.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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, have been hospitalized for and/or treated with 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, omega-3 fatty acids
• Have received any of the following; biologics in the last 6 months, methotrexate in 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; an active draining fistula as the primary manifestation of CD, documented short bowel syndrome, a stoma, 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, CNS, pulmonary, hematological, immunological, vascular and gastrointestinal disease in addition to CD,current malignancy or malignancy within 5 years prior to screening

Please refer to this study by ClinicalTrials.gov identifier  NCT00132899

Marybeth Hopkins, RN      (519) 663-3400  Ext. 33125    mhopkins@robarts.ca
Peggy K Vandervoort, RN, M.Sc.      (519) 663-3400-  Ext. 33783    pvandervoort@robarts.ca

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

Study chairs or principal investigators

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

Study ID Numbers:  RP0401
Last Updated:  August 19, 2005
Record first received:  August 19, 2005
ClinicalTrials.gov Identifier:  NCT00132899
Health Authority: United States: Institutional Review Board; Canada: Health Canada
ClinicalTrials.gov processed this record on 2005-08-23