Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease

Meissner, H.C., Groothuis, J.R., Rodriguez, W.J., Welliver, R.C., Hogg, G., Gray, P.H., Loh, R., Simoes, E.A.F., Sly, P., Miller, A.K., Nichols, A.I., Jorkasky, D.K., Everitt, D.E. and Thompson, K.A. (1999) Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease. Antimicrobial Agents and Chemotherapy, 43 5: 1183-1188.

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Author Meissner, H.C.
Groothuis, J.R.
Rodriguez, W.J.
Welliver, R.C.
Hogg, G.
Gray, P.H.
Loh, R.
Simoes, E.A.F.
Sly, P.
Miller, A.K.
Nichols, A.I.
Jorkasky, D.K.
Everitt, D.E.
Thompson, K.A.
Title Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
1098-6596
Publication date 1999-05
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 43
Issue 5
Start page 1183
End page 1188
Total pages 6
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty- three infants who were either delivered prematurely (≤35 weeks' gestation) or exhibited bronchopulmonary dysplasia were administered either single or repeat (two doses, 8 weeks apart) intramuscular injections of SB 209763 at a concentration of 0.25, 1.25, 5.0, or 10.0 mg/kg or of a placebo. Four of 229 adverse events were considered related to the study drug, including purpura (n = 3) and thrombocytosis (n = 1). No subject developed a detectable level of anti-SB 209763 antibody. Approximately 1 week after administration of the second dose of SB 209763 at 10 mg/kg, the mean plasma concentration (n = 9) was 68.5 μg/ml. The terminal half-life (T(1/2)) determined by noncompartmental analysis ranged from 22 to 50 days. The population pharmacokinetics for SB 209763 following intramuscular administration was appropriately described by a one-compartment model with first-order input and elimination. Higher values for clearance and volume of distribution at steady state were observed for younger patients, with values decreasing to 0.143 (ml/h)/kg and 161 mL/kg, respectively, by a mean age of 298 days (~10 months). The mean T(1/2) of SB 209763 for the study population was 32.5 days. No other factor (dose, weight, gender, race, premature birth, or bronchopulmonary dysplasia) was observed to alter the population pharmacokinetics of SB 209763 in this study of infants and young children. The mean neutralization titer on day 6 was 286, and the mean fusion inhibition titer was 36. At least 57% of subjects dosed at 1.25 to 10.0 mg of SB 209763 per kg of body weight who were seronegative at baseline experienced a fourfold or greater increase in fusion inhibition titer. Nine RSV infections were documented during the 16-week course of the study; the numbers of RSV infections were similar for the different regimens, including the placebo. The doses of SB 209763 studied may have been insufficient to confer protection against RSV lower respiratory tract disease; these results suggest that additional trials using higher doses of monoclonal antibody for immunoprophylaxis should be considered.
Keyword Immune globulin
Cotton rats
Infection
RSHZ19
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 17 Nov 2010, 11:39:10 EST