Literature DB >> 19258920

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.

Katia Abarca1, Elizabeth Jung, Pilar Fernández, Liang Zhao, Brian Harris, Edward M Connor, Genevieve A Losonsky.   

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.

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Year:  2009        PMID: 19258920     DOI: 10.1097/INF.0b013e31818ffd03

Source DB:  PubMed          Journal:  Pediatr Infect Dis J        ISSN: 0891-3668            Impact factor:   2.129


  16 in total

1.  Safety and pharmacokinetics of single intravenous dose of MGAWN1, a novel monoclonal antibody to West Nile virus.

Authors:  John H Beigel; Jeffrey L Nordstrom; Stanley R Pillemer; Cory Roncal; D Ronald Goldwater; Hua Li; P Chris Holland; Syd Johnson; Kathryn Stein; Scott Koenig
Journal:  Antimicrob Agents Chemother       Date:  2010-03-29       Impact factor: 5.191

Review 2.  Motavizumab.

Authors:  Oya Cingoz
Journal:  MAbs       Date:  2009-09-10       Impact factor: 5.857

Review 3.  Giving monoclonal antibodies to healthy volunteers in phase 1 trials: is it safe?

Authors:  Elizabeth Tranter; Gary Peters; Malcolm Boyce; Steve Warrington
Journal:  Br J Clin Pharmacol       Date:  2013-08       Impact factor: 4.335

4.  Respiratory syncytial virus infection of newborn CX3CR1-deficient mice induces a pathogenic pulmonary innate immune response.

Authors:  Sudipta Das; Mahesh Raundhal; Jie Chen; Timothy B Oriss; Rachael Huff; John V Williams; Anuradha Ray; Prabir Ray
Journal:  JCI Insight       Date:  2017-09-07

5.  Identification of residues in the human respiratory syncytial virus fusion protein that modulate fusion activity and pathogenesis.

Authors:  Anne L Hotard; Sujin Lee; Michael G Currier; James E Crowe; Kaori Sakamoto; Dawn C Newcomb; R Stokes Peebles; Richard K Plemper; Martin L Moore
Journal:  J Virol       Date:  2014-10-22       Impact factor: 5.103

Review 6.  Pharmacologic advances in the treatment and prevention of respiratory syncytial virus.

Authors:  Kerry M Empey; R Stokes Peebles; Jay K Kolls
Journal:  Clin Infect Dis       Date:  2010-05-01       Impact factor: 9.079

7.  A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season.

Authors:  Pilar Fernández; Adrian Trenholme; Katia Abarca; M Pamela Griffin; Micki Hultquist; Brian Harris; Genevieve A Losonsky
Journal:  BMC Pediatr       Date:  2010-06-03       Impact factor: 2.125

8.  A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults.

Authors:  Gabriel J Robbie; Ryan Criste; William F Dall'acqua; Kathryn Jensen; Nita K Patel; Genevieve A Losonsky; M Pamela Griffin
Journal:  Antimicrob Agents Chemother       Date:  2013-09-30       Impact factor: 5.191

Review 9.  Pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of monoclonal antibodies in children.

Authors:  Helena Edlund; Johanna Melin; Zinnia P Parra-Guillen; Charlotte Kloft
Journal:  Clin Pharmacokinet       Date:  2015-01       Impact factor: 5.577

Review 10.  The use of humanized monoclonal antibodies for the prevention of respiratory syncytial virus infection.

Authors:  Marcello Lanari; Silvia Vandini; Santo Arcuri; Silvia Galletti; Giacomo Faldella
Journal:  Clin Dev Immunol       Date:  2013-06-11
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