Abstract 969 Poster Session IV, Tuesday, 5/4 (poster 87)

Palivizumab, a humanized monoclonal antibody to the F-protein of RSV, is approved for intramuscular administration for prophylaxis of serious RSV disease in high risk children. Intravenous (IV) administration of reconstituted lyophilized palivizumab has not been previously studied. For IV administration palivizumab is reconstituted with 5 ml diluent for a final concentration of 20 mg/ml. In a pilot study 6 healthy adult volunteers received a single IV infusion (1-2 ml/minute) of 15 mg/kg reconstituted lyophilized palivizumab administered using a 0.22μ filter. Volunteers tolerated the agent well. In a subsequent study, 12 healthy adult volunteers received a single IV infusion (1-2 ml/minute) of either 15 mg/kg (4) or 30 mg/kg (8) which was not filtered. Two volunteers did not complete infusions as a result of acute "allergic" manifestations, including pruritis, urticaria, erythema, chest tightness. These rapidly resolved without treatment. Two other volunteers who completed infusions reported mild rash or pruritus. This study was repeated, but included pre- filtering (0.22μ) of the agent. All volunteers tolerated the infusion well, without any evidence of allergic reactions. Serum concentrations were similar in volunteers who received palivizumab through a filter and those who did not. The mean serum concentrations (SE) one hour and 30 days following 15 mg/kg were 379.3 (22.3) and 64.5 (10.2) ug/ml, respectively; following 30 mg/kg they were 804.0 (39.7) and 116.9 (8.2) ug/ml, respectively. Lastly, 21 children with prematurity or bronchopulmonary dysplasia were randomized into a study to receive 15 mg/kg (11) or 30 mg/kg (10) as a single IV infusion following filtration (0.22μ). Infusions were safe and well tolerated. Adverse events were similar in the 15 and 30 mg/kg groups and typical of what is expected in this population. The mean serum concentrations (SE) one hour and 30 days following 15 mg/kg were 302.7 (14.0) and 48.4 (3.1) ug/ml, respectively; following 30 mg/kg they were 599.3 (59.4) and 97.3 (17.6) ug/ml, respectively. Intravenous infusion of 15 and 30 mg/kg reconstituted lyophilized palizivumab using a 0.22μ filter was safe and well tolerated.

Funded by MedImmune, Inc.