Phase III Randomized Study of Anti-Tumor Necrosis Factor Chimeric Monoclonal Antibody (cA2) for Patients With Enterocutaneous Fistulae as a Complication of Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
OBJECTIVES: I. Evaluate the efficacy of chimeric monoclonal antibody (cA2) compared with placebo in closure of enterocutaneous fistulae in patients with Crohn's disease.

Detailed Description
-----------------
PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are stratified according to investigational site and number of fistulae (single vs multiple). Patients are randomized to one of three treatment arms: Arm I: Patients receive an infusion of chimeric monoclonal antibody (cA2) on weeks 0, 2, and 6. Arm II: Patients receive an infusion of cA2 on weeks 0 and 2, and an infusion of placebo on week 6. Arm III: Patients receive an infusion of placebo on day 1 of weeks 0, 2, and 6. Patients are followed every month for 3 months, then every 6-12 months for up to 2 years.

Conditions
-----------------
Crohn's Disease

Intervention / Treatment
-----------------
* Drug: monoclonal antibody cA2


Participation Criteria
=================
Eligibility Criteria
-----------------
PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Crohn's disease of at least 3 months duration confirmed by radiography or endoscopy Single or multiple draining enterocutaneous (including perianal) fistulae of at least 3 months duration All fistulae separate and distinctly identifiable No local complications of Crohn's disease such as strictures or abscesses --Prior/Concurrent Therapy-- Biologic therapy: No prior chimeric monoclonal antibody (cA2) At least 3 months since treatment with other therapeutic agent targeted at reducing tumor necrosis factor (e.g., pentoxifylline or thalidomide) At least 4 weeks since cyclosporine Chemotherapy: Concurrent methotrexate permitted if treatment began at least 3 months prior to enrollment, dose has been stable for at least 4 weeks prior to enrollment and remains stable throughout study period Otherwise, no methotrexate within 4 weeks prior to enrollment Concurrent 6-mercaptopurine or azathioprine permitted if treatment began at least 6 months prior to enrollment, dose has been stable for at least 8 weeks prior to enrollment, and remains stable throughout study period Otherwise, no 6-mercaptopurine or azathioprine within 4 weeks prior to enrollment Endocrine therapy: Concurrent corticosteroids (e.g., oral prednisone) permitted if dose has been stable for at least 3 weeks prior to enrollment, does not exceed 40 mg/kg, and remains stable throughout study period (dosage may be tapered after 6 weeks for some patients) Otherwise, no corticosteroids within 4 weeks prior to enrollment Other: Concurrent antibiotics or aminosalicylates for Crohn's disease permitted if dose has been stable for at least 4 weeks prior to enrollment and remains stable throughout study period Otherwise, no antibiotics or aminosalicylates within 4 weeks prior to enrollment At least 3 months since investigational drugs --Patient Characteristics-- Hematopoietic: WBC at least 3,500/mm3 Neutrophil count at least 1,500/mm3 Lymphocyte count at least 500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 8.5 g/dL No severe, progressive, or uncontrolled hematologic disease Hepatic: SGOT no greater than 3 times upper limit of normal (ULN) Alkaline phosphatase no greater than 3 times ULN No severe, progressive, or uncontrolled hepatic disease Renal: Creatinine no greater than 1.7 mg/dL No severe, progressive, or uncontrolled renal disease Cardiovascular: No severe, progressive, or uncontrolled cardiac disease Pulmonary: No severe, progressive, or uncontrolled pulmonary disease Neurologic: No severe, progressive, or uncontrolled neurologic or cerebral disease Other: Negative pregnancy test required and no planned pregnancy within 7.5 months following first infusion Effective contraception required of fertile patients during and for 6 months after study No severe, progressive, or uncontrolled endocrine disease No serious infections (e.g., hepatitis, pneumonia, pyelonephritis) within prior 3 months No history of opportunistic infections (e.g., herpes zoster) within 2 months No allergy to murine proteins No active cytomegalovirus, Pneumocystis carinii, or drug resistant atypical mycobacterial infections No recent drug or alcohol abuse No HIV infection, ARC (AIDS-related complex) or AIDS Total parenteral nutrition or tube feeding not permitted No prior or concurrent malignancy within 5 years

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: monoclonal antibody cA2|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Crohn's disease, gastrointestinal disorders, rare disease