Safety and pharmacokinetics of palivizumab therapy in children hospitalized with respiratory syncytial virus infection

Background: Respiratory syncytial virus (RSV) infection represents a major cause of pediatric respiratory hospitalizations. Limited treatment options exist. Palivizumab is a humanized monoclonal IgG1 antibody to the fusion protein of RSV that is highly active against RSV A and B strains. Methods: A phase I/II, multicenter, randomized, double-blind, placebo-controlled, escalating dose clinical trial to describe the safety, tolerance, pharmacokinetics and clinical outcome of a single intravenous dose of palivizumab in previously healthy children hospitalized with acute RSV infection. Results: Fifty-nine children :52 years of age received study drug. Sixteen children received 5 mg/kg of palivizumab (n = 8) or placebo (n = 8); 43 received 15 mg/kg of palivizumab (n = 22) or placebo (n = 2 1). Adverse events judged to be related to study drug were seen in one 5-mg/kg palivizumab patient and one 15-mg/kg palivizumab patient. These events were transient or consistent with progression of RSV disease. No discontinuations of study drug infusion because of adverse events occurred. Mean serum concentrations of palivizumab in the 5- and 15-mg/kg groups, respectively, were 61.2 and 303.4 mug/mL at 60 min and 11.2 and 38.4 mug/mL after 30 days. There were no significant differences in clinical outcomes between placebo and palivizumab groups for either dose. Conclusions: Intravenous palivizumab was safe and well-tolerated in children hospitalized with RSV disease. A single 15-mg/kg dose achieved serum palivizumab concentrations above the 25- to 30-mug/mL concentration associated with 2-log reduction of pulmonary RSV titer in the cotton rat model.