A Phase 3 Safety and Efficacy Study of Baloxavir Marboxil in Children Less Than 1 Year Old With Suspected or Confirmed Influenza

Abstract

Background: Baloxavir marboxil (baloxavir) inhibits influenza virus cap-dependent endonuclease and has demonstrated safety and efficacy in children 1-<12 years of age. This study assessed the safety and efficacy of baloxavir in children <1 year old. Methods: miniSTONE-1 (NCT03653364) was a Phase III, global, multicenter, single-arm study to evaluate patients <1 year of age who received a single dose of baloxavir (age ≥3 months: 2 mg/kg; <3 months 1 mg/kg). The primary endpoint was safety; secondary endpoints included pharmacokinetics and efficacy (time to alleviation of signs and symptoms, duration of fever and symptoms, antibiotic use and cessation of viral shedding). Results: Overall, 48/49 enrolled patients received baloxavir, of whom 15 had positive centralized influenza reverse transcription polymerase chain reaction tests and comprised the intent-to-treat influenza-infected population. The median age was 6 months and 79.2% of patients were not influenza-vaccinated. Overall, 51 adverse events (AEs) were reported in 23 patients; most were grade 1-2. The most common AEs were diarrhea (16.7%) and vomiting (12.5%). Two patients experienced serious AEs unrelated to treatment. In the intent-to-treat influenza-infected population, median time to alleviation of signs and symptoms was 163.7 hours [95% confidence interval (CI): 122.5-not estimable], median duration of fever was 23.1 hours (95% CI: 22.3-44.6) and median time to cessation of viral shedding was 24.5 hours (95% CI: 24.2-68.6). Conclusions: Baloxavir was well tolerated in children <1 year of age, with no new safety signals identified. Clinical, virological and safety outcomes were consistent with established profiles in adults, adolescents and children 1-<12 years old.