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

• Status: Completed
• Trial end date: 1996-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: FDA Office of Orphan Products Development
• Collaborator: Centocor, Inc.
• Treatments: Antibodies; Antibodies, Monoclonal; Immunoglobulins; Infliximab

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