SAFETY, TOLERANCE AND PHARMACOKINETICS OF A HUMANIZED MONOCLONAL-ANTIBODY TO RESPIRATORY SYNCYTIAL VIRUS IN PREMATURE-INFANTS AND INFANTS WITH BRONCHOPULMONARY DYSPLASIA

Background. Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants. MEDI-493 (palivizuma b) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replicatio n. Objectives. To describe the safety, tolerance, immunogenicity and p harmacokinetics of repeat intravenous doses of MEDI-493 in premature i nfants or infants with bronchopulmonary dysplasia. Design. Phase IIII multicenter, randomized, double blind, placebo-controlled, dose escala tion trial. Patient population. Infants born prematurely (less than or equal to 35 weeks of gestation) who were less than or equal to 6 mont hs of age and infants with bronchopulmonary dysplasia who were less th an or equal to 24 months of age were eligible for study participation. Study agents. Participants received 3, 10 or 15 mg/kg MEDI-493 or 0.9 % saline intravenously every 30 days for up to five doses. Results. ME DI-493 was safe and well-tolerated and did not induce a specific anti- MEDI-493 response. The mean half-life of 20 days was comparable with t hat of other immunoglobin G preparations. Mean trough serum concentrat ions 30 days after Infusion 1 were 6.8, 36.1 and 60.6 mu g/ml for the 3-, 10- and 15-mg/kg dose groups, respectively. After Infusion 2 the t rough concentrations were 11.9, 45.2 and 70.7 mu g/ml. After subsequen t doses the mean trough values ranged from 14 to 18 mu g/ml in those g iven 3 mg/kg and were >40 mu g/ml far patients who received 10 or 15 m g/kg MEDI-493 (46 to 72 mu g/ml and 88 to 96 mu g/ml, respectively). C onclusions. MEDI-493 was safe and well-tolerated in this high risk ped iatric population. Mean serum concentrations of MEDI-493 that have bee n shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when In or 15 mg/kg MEDI-493 was given every 30 d ays to pediatric patients at high risk for serious RSV disease, Monthl y doses of 15 mg/kg maintained concentrations of >40 mu g/ml for the m ajority of patients.