title: Randomized, Double-Blind Study of the Safety of the Liquid Versus Lyophilized Formulation of Palivizumab in Premature Infants and Children with Chronic Lung Disease of Prematurity.
abstract: BACKGROUND
  To avoid the need for reconstitution required by lyophilized palivizumab, a liquid formulation was developed. This study assessed the safety and antidrug antibodies (ADA) of the liquid formulation of palivizumab compared with the lyophilized formulation.
  
  
  METHODS
  This phase 4, randomized, double-blind, multicenter study included children with chronic lung disease of prematurity who were ≤24 months of age and children born prematurely with a gestational age of ≤35 weeks who were ≤6 months of age at randomization. Subjects were randomized 1:1 to 15 mg/kg of either liquid or lyophilized palivizumab administered via intramuscular injection every 30 days for a total of 5 injections. Safety was assessed based on serious adverse events (SAEs). ADA to palivizumab was assessed using blood collected at baseline and at a time point between study days 240 and 300.
  
  
  RESULTS
  A total of 413 subjects were included in the analyses. The incidence of SAEs reported was 8.5% with liquid palivizumab and 5.9% with lyophilized palivizumab; none were deemed drug-related. The reported SAEs were consistent with expected conditions in this pediatric age group; there was no increase in respiratory syncytial virus (RSV) disease with liquid palivizumab. At study days 240-300, antipalivizumab antibodies were detected in none of the subjects in the liquid palivizumab group and in 1 subject in the lyophilized group. The true ADA percent positive, based on the upper limit of the 95% confidence interval (CI), was <1.5% for both treatments combined.
  
  
  CONCLUSIONS
  The frequency of detection of ADAs was low. The true ADA percent positive for both treatment groups combined based on the upper limit of the 95% CI was <1.5%. The type and frequency of SAEs reported were as expected, and there was no evidence of an increase in RSV disease with liquid palivizumab.
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Doris
authors.initials: D
authors.lastname: Makari
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Jensen
authors.affiliation: MedImmune, Gaithersburg, MD, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Harris
authors.affiliation: MedImmune, Gaithersburg, MD, USA. jafrih@medimmune.com.
authors.forename: Hasan S
authors.initials: HS
authors.lastname: Jafri
keywords: Antidrug antibody; Children; Chronic lung disease of prematurity; Liquid; Lyophilized; Palivizumab; Premature infants; Respiratory syncytial virus disease; Safety