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

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.

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.

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]).

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.

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