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