Safety, tolerability, pharmacokinetics, and immunogenicity of motavizumab, a humanized, enhanced-potency monoclonal antibody for the prevention of respiratory syncytial virus infection in at-risk children.

Abstract

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.

• Authors: Katia Abarca, Elizabeth Jung, Pilar Fernández, Liang Zhao, Brian Harris, Edward M Connor, Genevieve A Losonsky, Motavizumab Study Group
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 28 Issue 4 Pg. 267-72 (Apr 2009) ISSN: 0891-3668 [Print] United States
• PMID: 19258920 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antiviral Agents
• motavizumab
• Palivizumab

Topics

• Antibodies, Monoclonal (administration & dosage, adverse effects, immunology, pharmacokinetics, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antiviral Agents (administration & dosage, adverse effects, immunology, pharmacokinetics)
• Chronic Disease
• Double-Blind Method
• Humans
• Infant
• Infant, Newborn
• Infant, Premature
• Infant, Premature, Diseases (prevention & control)
• Injections, Intramuscular
• Lung Diseases
• Male
• Palivizumab
• Respiratory Syncytial Virus Infections (prevention & control)
• Risk Factors