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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: 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, 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. 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 <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.

SUBMITTER: Makari D

PROVIDER: S-EPMC4269632 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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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.

Makari Doris D Jensen Kathryn M KM Harris Brian B Jafri Hasan S HS

Infectious diseases and therapy 20140826 2

<h4>Introduction</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 25156956

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Project description:ImportanceMost premature infants will not develop retinopathy of prematurity (ROP) of clinical relevance, yet screening evaluations often continue beyond hospital discharge, even for those infants without ROP.ObjectivesTo identify the characteristics of infants at low risk for ROP, for whom further postdischarge screening may be of limited value.Design, setting, and participantsThis study took place in North American neonatal intensive care units where clinicians had expertise in ROP. Infants with birth weight less than 1251 g who were born at or transferred into an Telemedicine Approaches to Evaluating Acute-Phase ROP (e-ROP) study center were enrolled. The study included post hoc analysis of prospectively collected in-hospital ROP examination results among infants enrolled in the e-ROP study. We characterized infants without ROP and performed logistic regression on the subset of infants who were 27 to 33 weeks' gestational age to determine characteristics associated with the absence of ROP during all in-hospital examinations.Main outcomes and measuresThe main measure was the absence of ROP prior to hospital discharge; the main outcome was treatment for ROP.ResultsA total of 1257 infants born at 22 to 35 weeks' gestation (median [interquartile range (IQR)], 26 [25-28] weeks) with birth weights less than 1251 g (median [IQR], 860 [690-1040] g) underwent 4113 ROP examinations between 31 and 47 weeks' postmenstrual age. Overall, 1153 examinations (38%) showed no ROP, and 456 infants (36%) did not have ROP prior to study center discharge or study end point. Among infants without ROP during examinations at 32 and 33 weeks' postmenstrual age, 16 (9.4%) and 14 (5.3%) subsequently underwent ROP treatment, respectively. At hospital discharge, there was no ROP in 59% of infants of 27 to 33 weeks' gestational age, compared with 15% of those who were less than 27 weeks' gestational age (difference, 44% [95% CI, 38.5%-48.1%]; P ≤ .001). With more than 85% follow-up among infants without ROP by 37 weeks' postmenstrual age, none (95% CI, 0%-0.98%) were treated for ROP. In multivariate analysis of infants born at 27 to 33 weeks' gestation, larger birth weight (OR, 4.1 [95% CI, 1.6-10.3]) and higher gestational age (OR, 4.0 [95% CI, 1.5-10.8]) were significantly associated with absence of ROP.Conclusions and relevanceThese findings suggest that, for infants of 27 weeks' gestational age or greater and birth weights larger than 750 g, if no ROP has been detected by discharge at near-term postmenstrual age, then further ROP surveillance has limited value. Studies of all infants at risk are needed to develop more specific, objective criteria for termination of ROP surveillance and focus resources on infants at higher risk of ROP.Trial registrationClinicalTrials.gov Identifier: NCT01264276.

Project description:Respiratory syncytial virus (RSV) is an important pathogen causing annual epidemics of bronchiolitis and pneumonia among infants worldwide. High-risk infants currently receive RSV prophylaxis with palivizumab, a humanized RSV monoclonal antibody (MAb). In preclinical in vitro and in vivo (cotton-rat model) studies, motavizumab, a new RSV MAb, was shown to have greater anti-RSV activity than palivizumab. Motavizumab is currently under review for licensing approval. Since both MAbs may be available concurrently, this study evaluated their safety and tolerability when administered sequentially during the same RSV season.Between April 2006 and May 2006, 260 high-risk infants were randomly assigned 1:1:1 to receive monthly intramuscular injections: 2 doses of motavizumab followed by 3 doses of palivizumab (M/P); 2 doses of palivizumab followed by 3 doses of motavizumab (P/M); or 5 doses of motavizumab (control). Adverse events (AEs, serious AEs [SAEs]), development of antidrug antibody (ADA), and serum drug trough concentrations were assessed.Most children received all 5 doses (246/260 [94.6%]) and completed the study (241/260 [92.7%]). While overall AE rates were similar (mostly level 1 or 2 in severity), SAEs and level 3 AEs occurred more frequently in the M/P group (SAEs: 22.9% M/P, 8.4% P/M, 11.8% motavizumab only; level 3 AEs: 15.7% M/P, 6.0% P/M, 6.5% motavizumab only). This trend in AE rates occurred before and after switching from motavizumab to palivizumab, suggesting a cause other than the combined regimen. Frequencies of AEs judged by the investigator to be related to study drug were similar among groups. Two deaths occurred on study (both in the M/P group, before palivizumab administration); neither was considered by the site investigator to be related to study drug. Mean serum drug trough concentrations were comparable among groups; ADA detection was infrequent (5.1% or less of any group).The conclusions drawn from this study are limited by the small sample size per group. However, within this small study, overall AE rates, serum drug trough concentrations, and development of ADA associated with administering motavizumab and palivizumab sequentially to high-risk children appear comparable to administering motavizumab alone during the same RSV season.clinicaltrials.gov NCT00316264.

Dataset Information

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.

Publications

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.

Similar Datasets

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