Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group.
Pediatr Infect Dis J
; 17(2): 110-5, 1998 Feb.
Article
in En
| MEDLINE
| ID: mdl-9493805
ABSTRACT
BACKGROUND:
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants. MEDI-493 (palivizumab) is a humanized monoclonal antibody to the fusion protein of RSV and is active in animal models for prevention of pulmonary RSV replication.OBJECTIVE:
To describe the safety, tolerance, immunogenicity and pharmacokinetics of repeat intravenous doses of MEDI-493 in premature infants or infants with bronchopulmonary dysplasia.DESIGN:
Phase I/II multicenter, randomized, double blind, placebo-controlled, dose escalation trial. PATIENT POPULATION Infants born prematurely (< or = 35 weeks of gestation) who were < or = 6 months of age and infants with bronchopulmonary dysplasia who were < or = 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:
MEDI-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 that of other immunoglobulin G preparations. Mean trough serum concentrations 30 days after Infusion 1 were 6.8, 36.1 and 60.6 microg/ml for the 3-, 10- and 15-mg/kg dose groups, respectively. After Infusion 2 the trough concentrations were 11.9, 45.2 and 70.7 microg/ml. After subsequent doses the mean trough values ranged from 14 to 18 microg/ml in those given 3 mg/kg and were > 40 microg/ml for patients who received 10 or 15 mg/kg MEDI-493 (46 to 72 microg/ml and 88 to 96 microg/ml, respectively).CONCLUSIONS:
MEDI-493 was safe and well-tolerated in this high risk pediatric population. Mean serum concentrations of MEDI-493 that have been shown to produce a 2-log reduction in pulmonary RSV titer in cotton rats were maintained when 10 or 15 mg/kg MEDI-493 was given every 30 days to pediatric patients at high risk for serious RSV disease. Monthly doses of 15 mg/kg maintained concentrations of > 40 microg/ml for the majority of patients.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Syncytial Viruses
/
Bronchopulmonary Dysplasia
/
Viral Fusion Proteins
/
Respiratory Syncytial Virus Infections
/
Antibodies, Monoclonal
Type of study:
Clinical_trials
Limits:
Humans
/
Newborn
Language:
En
Journal:
Pediatr Infect Dis J
Journal subject:
DOENCAS TRANSMISSIVEIS
/
PEDIATRIA
Year:
1998
Document type:
Article
Affiliation country:
Estados Unidos
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA