A Phase 3 Study of Ensitrelvir in Japanese Participants Aged 6-11 Years with SARS-CoV-2 Infection.

Abstract

Background: Children aged <12 years with coronavirus disease 2019 (COVID-19) have limited treatment options; currently approved oral antivirals are restricted by age or bodyweight. We evaluated the safety and plasma concentration-time profiles and exploratory efficacy of ensitrelvir, a once-daily oral 3C-like protease inhibitor, in children with mild-to-moderate COVID-19 in Japan.

Methods: This phase 3, double-blind, placebo-controlled study randomized (2:1) participants aged 6 to <12 years presenting ≤72 h after COVID-19 onset to receive ensitrelvir (bodyweight-based dosing) or placebo once daily for 5 days. Primary endpoints were safety and pharmacokinetics. Secondary endpoints included change in viral ribonucleic acid (RNA) and time to resolution (TTR) of key COVID-19 symptoms (stuffy or runny nose and cough) plus fever.

Results: Of 117 randomized participants (median age 10 years), 78 received ensitrelvir and 39 received placebo. Ensitrelvir was well tolerated with no new safety concerns. Plasma concentration-time profiles were similar across bodyweight categories (20 to <30, 30 to <40, and ≥40 kg). Ensitrelvir reduced viral RNA vs placebo on Day 4, by approximately 1.0 log10 copies/mL (95% CI, -1.45 to -0.47). Median TTR of key COVID-19 symptoms was 140.5 h with ensitrelvir and 146.2 h with placebo (median difference -5.7 h [95% CI, -73.6 to 43.4 h]).

Conclusions: In children aged 6 to <12 years with mild-to-moderate COVID-19 treated with ensitrelvir, we observed a favorable safety profile, adult-matched plasma concentration-time profile, and a greater reduction in viral RNA vs placebo. Ensitrelvir represents a potential treatment option for underserved pediatric patients with mild-to-moderate COVID-19.

Clinical trial registration: Japan Registry of Clinical Trials, jRCT2031230140 (https://jrct.mhlw.go.jp/en-latest-detail/jRCT2031230140).