Safety and Pharmacokinetics of the RSV Fusion Inhibitor Sisunatovir Across Two Early-phase Studies in Infants and Children With RSV Lower Respiratory Tract Infection

BACKGROUND: Sisunatovir is an investigational respiratory syncytial virus (RSV) antiviral that was effective in an adult human viral challenge study. METHODS: In 2 multicenter studies, safety and pharmacokinetics of sisunatovir were evaluated in hospitalized individuals 1 month to 36 months of age (Study 1) and outpatient and hospitalized individuals 1 day to 60 months of age (Study 2) with RSV lower respiratory tract infection (RSV-LRTI). In Study 1 Part A, participants received single sisunatovir doses; in Part B, participants received placebo or multiple ascending sisunatovir doses every 12 hours for 5 days. In Study 2, participants received weight-based sisunatovir dosing or placebo every 12 hours for 5 days. RESULTS: In Study 1 Part A, 19 participants received sisunatovir; 31 in Part B received sisunatovir (n = 22) or placebo (n = 9). Adverse events (AEs) were reported by 11 (57.9%) and 12 (38.7%) participants in Parts A and B, respectively. In Study 2, 10 participants received sisunatovir (n = 6) or placebo (n = 4). No treatment-related serious AEs were reported; all AEs were mild or moderate. In Study 1 Part A 12 hours post-dose, mean sisunatovir concentrations were within safety margins. In Part B, at the highest dose assessed for each group, steady-state trough concentrations surpassed those effective in the adult challenge study. CONCLUSIONS: In children with RSV-LRTI, sisunatovir was safe and well tolerated. The pediatric multiple-dose regimen achieved plasma concentrations effective at reducing viral load and symptoms in an adult challenge study; however, further studies are needed to identify doses providing comparable exposure across pediatric populations. CLINICALTRIALSGOV REGISTRATION NUMBER: NCT04225897 (registered December 11, 2019); NCT06102174 (registered October 6, 2023).