RESUMO
Previously healthy children hospitalized with respiratory syncytial virus (RSV) received motavizumab (3, 15, or 30 mg/kg intravenously), an RSV-specific monoclonal antibody, or placebo. Safety, tolerability, motavizumab concentrations, and immunogenicity were assessed. Cultivatable RSV in the upper respiratory tract was significantly reduced with motavizumab compared with placebo day 1 post-treatment. No adverse events were considered motavizumab-related by site investigators.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Antivirais/efeitos adversos , Antivirais/farmacologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/farmacologia , Antivirais/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Placebos/administração & dosagem , Vírus Sincicial Respiratório Humano/imunologia , Sistema Respiratório/virologiaRESUMO
BACKGROUND: : Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children. Motavizumab is an investigational humanized monoclonal antibody for RSV prophylaxis. METHODS: : A dose-escalation study was conducted followed by assessment of safety, tolerability, serum concentrations, and immunogenicity during a second consecutive RSV season. In season 1, premature infants aged < or =6 months or children < or =24 months with chronic lung disease of prematurity received monthly motavizumab (3 or 15 mg/kg). In season 2, children who received > or =3 motavizumab doses in season 1 were randomized to receive monthly motavizumab or palivizumab 15 mg/kg. RESULTS: : Of 217 children enrolled in season 1, 211 (97.2%) received motavizumab 15 mg/kg and 205 (94.5%) patients completed the study through 90 days after the final dose. In season 2, 136 children were randomized to receive motavizumab (n = 66) or palivizumab (n = 70). The most commonly reported related adverse event was transient injection site erythema. In season 1, mean trough motavizumab concentrations were 7.9 and 50.2 microg/mL after the 3- and 15-mg/kg doses, respectively. Trough concentrations increased with repeated motavizumab dosing; a similar pattern was seen in season 2. Antimotavizumab reactivity occurred infrequently (3.3%) in season 1. In season 2, no treatment group-specific antidrug antibody was detected through 90 to 120 days after dosing with either product. CONCLUSIONS: : The pharmacokinetic profile of motavizumab was similar to that of other IgG1 antibodies. Increased adverse reactions or immunogenicity were not observed during and after a second season of treatment with motavizumab. Safety findings from these studies supported the continued development of motavizumab.
Assuntos
Anticorpos Monoclonais , Antivirais , Doenças do Prematuro/prevenção & controle , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/imunologia , Antivirais/farmacocinética , Doença Crônica , Método Duplo-Cego , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Injeções Intramusculares , Pneumopatias , Masculino , Palivizumab , Fatores de RiscoRESUMO
OBJECTIVES: To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD). STUDY DESIGN: A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization. RESULTS: Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV hospitalization per 100 children (P=.003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P=.014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups. CONCLUSIONS: Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.