Abstract
BackgroundRespiratory 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.MethodsBetween 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.ResultsMost 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).ConclusionsThe 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.Trial Registrationclinicaltrials.gov NCT00316264
Highlights
Respiratory syncytial virus (RSV) is an important pathogen causing annual epidemics of bronchiolitis and pneumonia among infants worldwide
There were 2 minor imbalances noted that were not felt to affect the outcome of the study: 1) the baseline incidence of chronic lung disease (CLD) was slightly lower in the M/P treatment group (13.3%) than in the P/M and motavizumab-only treatment groups (16.7% and 17.2%, respectively); and 2) there were slightly more male subjects enrolled in the M/ P treatment group (61% in M/P compared with 51% and 52% in the P/M and the motavizumab-only [control] groups, respectively)
Two children who had study drug discontinued due to serious AEs (SAEs) continued with follow-up until the completion of the study; both were in the M/P group
Summary
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). The greatest morbidity and mortality occur among children at high risk for severe RSV disease, including premature infants, infants with chronic lung disease (CLD), and infants with complicated congenital heart disease [4,5,6]. These high-risk infants currently receive prophylaxis for RSV with palivizumab (MedImmune, Gaithersburg, MD, USA), which is recommended and indicated for the prevention of severe RSV disease in high-risk children [7,8]. In the IMpact study, preterm infants without CLD who received prophylaxis with palivizumab had an even greater reduction in RSV-related hospitalizations that approached 80% [12]
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