An Open-Label, Multiple-Dose Study to Evaluate the Efficacy, Safety and Pharmacokinetics of BG9588 (Anti-CD40L Antibody) in Subjects With Proliferative Lupus Glomerulonephritis (SLE-GN)

Date de début de l'étude : 1 juin 1999

Must give written informed consent prior to any testing under this protocol. Must be 18 years or older, inclusive, at the time of informed consent. Must have a renal biopsy showing active WHO Class III, IV, or mixed membranous and proliferative SLE GN, within the 5 years prior to the first dose of study drug. Must have proteinuria of greater than or equal to 1.0 g/day at both the Day-27 and day-13 evaluations. Must fulfill any one the following four criteria, at each of the two screening visits (i.e., Day-27 and Day-13): Anti-dsDNA antibody greater than 2x the upper limit of normal (ULN). C3 complement less than 80 mg/dL. Hematuria greater than 5 rbc/hpf. Urinary granular or red blood cell casts. Must not have any medical disorder, which in the opinion of the investigator, should exclude the subject from this study. Must not have prior arterial or venous thrombosis, or history of recurrent abortion (3 or more), in the presence of anti-cardiolipin antibodies. Must not have a chest x-ray with evidence of active infection or neoplasm within the 6 months prior to the first dose of study drug. Must not have rapidly progressive glomerulonephritis, defined as a doubling of serum creatinine, within the 3 months prior to the first dose of study drug. Must not have fibrinoid necrosis and/or cellular crescents affecting more than 25 percent of glomeruli in any renal biopsy performed within the 3 months prior to the first dose of study drug. Must not have clinically significant findings for any of the following within the 4 weeks prior to the first dose of study drug: active psychiatric disease, serum creatinine greater than 2.0 mg/dL, prothrombin time (PT) greater than 1.3x control (in the absence of coumadin therapy; abnormal PT values due to anti-coagulation therapy are allowed if within the therapeutic range), AST or ALT levels greater than 3x normal, other major organ dysfunction, or serious local or systemic infection (e.g., pneumonia, septicemia). Must not be positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HVC Ab), or HIV antibody at the Day-27 evaluation. Must not have a mean CD4 count less than or equal to 300 microliters (mean of Day-27 and Day-13 results). Must not have treatment with an antibody or other investigational drug within the 3 months prior to the first dose of the study drug. Must not have any vaccination within the 4 weeks prior to the first dose of the study drug. Must not have treatment with IV or oral cyclophosphamide within the 4 weeks prior to the first dose of the study drug. Must not have treatment with any of the following medications within the 4 weeks prior to the first dose of study drug: IV methylprednisolone, cyclosporine or related compound, or oral prednisone (equivalent oral glucocorticoid) at a dose greater than 0.5 mg/kg/day. Must not have initiation of treatment with ACE inhibitors within the 4 weeks prior to the first dose of study drug. Must not have initiation of treatment with azathioprine, methotrexate or mycophenolate mofetil within the 4 weeks prior to the first dose of study drug. Must not have treatment with any new oral or new IV antibiotic within the 2 weeks prior to the first dose of study drug. Subjects on prophylactic antibiotics are permitted to continue these during the study. Female subjects, unless post-menopausal or surgically sterile, must use an adequate method of contraception. Women must not be currently breast-feeding. Must not have a positive pregnancy test in any evaluation prior to the first dose of study drug. Must not be currently enrolled in any other study in which the subject is receiving any type of drug or non-drug therapy. Must not have been previously dosed with BG9588.