Clinical Trial: BG9588 (Anti-CD40L Antibody) to Treat Lupus Nephritis
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: 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)
Brief Summary:
The purpose of this study is to investigate whether the experimental drug BG9588 can be used to treat lupus nephritis more effectively and with less toxicity than standard treatments, including cyclophosphamide (Cytoxan), azothioprine (Imuran) and prednisone.
The body's immune system naturally produces antibodies to fight foreign substances like bacteria and viruses. In autoimmune diseases like lupus, however, the body makes antibodies that attack its own tissues, causing inflammation and organ damage. Lupus antibodies attack and damage kidney cells. BG9588 can interfere with the production of these antibodies, and therefore, may lessen kidney damage in people with lupus nephritis.
This study will look at: how BG9588 enters and leaves the blood and body tissue over time; adverse effects of the drug; and whether treatment with BG9588 can result in less kidney damage than other therapies.
Study patients will be receive a 30-minute infusion of BG9588 into a vein every two weeks for three doses and then once every 28 days for four doses. Patients' steroid dosage may be tapered; individual adjustments will be made as required.
Patients screened for the study will undergo a physical examination, medical history, various blood and urine tests, as well as complete a quality of life questionnaire. Results of a previous kidney biopsy and chest X ray are also required. Many of these tests will be repeated throughout the study.
In a previous animal study, BG9588 treatment of mice with lupus nephritis improved their disease and survival.
Detailed Summary: Studies in animals and humans with lupus nephritis have demonstrated that essential role of CD40 ligand/CD40 interaction in the production of pathogenic autoantibodies. Anti-CD40L antibody treatment of mice with lupus nephritis ameliorates disease and improves survival. BG9588 is a recombinant humanized monoclonal antibody that specifically binds to CD40 ligand (CD40L) expressed on the surface of activated T lymphocytes and thereby blocks the CD40L/CD40 interaction between T and B cells that is required for the initiation for certain antibody responses. Available preclinical data indicates that BG9588 does not cause a global blockage of the immune response to pathogens and that its effects are reversible upon clearance from the systemic circulation. In this Phase I/II open-label, multiple-dose, multicenter study, 30 subjects with active proliferative lupus nephritis will receive 20 mg/kg BG9588 by IV infusion once every 14 days for three doses, and then once every 28 days for four doses for a total of 7 doses. The primary objective is to determine if BG9588 can decrease proteinuria by greater than or equal to 50 percent from baseline without worsening renal function. The secondary objectives are to determine the safety and pharmacokinetics of BG9588, as well as the effects of BG9588 on renal flares; cellular casts; C(3) levels and anti-dsDNA titers; requirement for prednisone; general lupus activity; and quality of life.
Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: November 3, 1999
Date Started: June 1999
Date Completion: May 2000
Last Updated: March 3, 2008
Last Verified: June 1999
