Phase I Trial of Recombinant Human Interleukin-10 (SCH 52000) in Patients With Wegener's Granulomatosis

The purpose of this study is to assess the safety, tolerance, and immunologic effects of interleukin-10 (IL-10), in patients with Wegener's granulomatosis. A secondary objective is to determine if IL-10 demonstrates sufficient anti-inflammatory activity in the treatment of Wegener's granulomatosis to warrant further study in a larger trial. In this study, IL-10 will be given either alone or in combination with standard therapeutic agents, usually consisting of cyclophosphamide, methotrexate, and/or prednisone. Patients will be eligible to receive IL-10 when there is evidence of active disease. IL-10 will be administered by subcutaneous injection at a dose of 4 µ (Micro)g/kg/day for 28 days.

The purpose of the study is to assess the safety, tolerance, and immunologic effects of interleukin-10 (IL-10), in patients with Wegener's granulomatosis. A secondary objective is to determine if IL-10 demonstrates sufficient anti-inflammatory activity in the treatment of Wegener's granulomatosis to warrant further study in a larger trial. In this study, IL-10 will be given either alone or in combination with standard therapeutic agents, usually consisting of cyclophosphamide, methotrexate, and/or prednisone. Patients will be eligible to receive IL-10 when there is evidence of active disease. IL-10 will be administered by subcutaneous injection at a dose of 4 µ (Micro)g/kg/day for 28 days.

Eligibility Criteria:
Diagnosis of Wegener's granulomatosis based on clinical characteristics and histopathological and/or angiographic evidence of vasculitis or the presence of glomerulonephritis and a positive assay for anti-neutrophil cytoplasmic autoantibodies (ANCA).

Age between 18 to 65 years.

No change in immunosuppressive drug therapy during the prior 4 weeks and one of the following:

Persistent disease activity ("Vasculitis Activity Index" score of greater than or equal to 3) despite optimal therapy;

Persistent or recurrent disease activity in a patient who cannot tolerate optimal therapy;

Patients not on maximal immunosuppressive therapy but with persistent or recurrent disease activity that is not, in the judgment of investigators, immediately threatening the function of a major organ system;

No evidence of active infection.

Patients may not be pregnant or nursing infants. Fertile women must have a negative pregnancy test within one week prior to study entry and all participants must be using effective means of birth control.

Serum creatinine is less than 3.5 mg/dL.

Hemocytopenia (platelet count is greater than 100,000/mm(3), leukocyte count is greater than 3,500/mm(s), hemoglobin is greater than 9 mg/dL).

Liver function test abnormalities is less than 3x upper limits of normal (either serum GOT, GPT, alkaline phosphatase, and/or bilirubin).

Patients cannot be anti-HIV, anti-HCV, or anti-Hepatitis B surface antigen (HBsAG) positive.

Weight greater less than 104 Kg (because of SCH 52000 concentration and volume limitations for subcutaneous injection).

No treatment with any investigational drug within 30 days.

No pre-existing malignancy.

No known allergy to E. coli protein or IL-10.

No history of psychiatric illness that in the opinion of the principal investigator would preclude entrance into the study.