Background. Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis®) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. Objective. To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. Design. A Phase I/II multicenter, open label, escalating dose clinical trial. Patient population and dosing regimen. Children (n = 65) born prematurely at ≤35 weeks of gestation who were ≤6 months of age (n = 41) and children with bronchopulmonary dysplasia who were ≤24 months of age (n = 24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n = 11), 10 mg/kg (n = 6) and 15 mg/kg (n = 48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. Results. The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 μg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 μg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of ~70 μg/ml. These concentrations were similar to previously published trough concentrations after iv administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. Conclusions. MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 μg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with iv administration of MEDI-493.
- Monoclonal antibody
- Respiratory syncytial virus
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Microbiology (medical)