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

Introduction: 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, doubleblind, 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 <.5% for both treatments combined. Conclusion: 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 <.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.