Nirmatrelvir/Ritonavir for the Treatment of COVID-19 in Children Aged 6 Years and Older.

Abstract

This ongoing phase 2/3 interventional, open-label study evaluated nirmatrelvir/ritonavir (NMV/r) in pediatric participants with mild-to-moderate COVID-19 at risk for severe disease (due to underlying medical conditions). Primary objectives were pharmacokinetics (PK) and safety. We report data from participants aged at least 6 years. Twice daily (BID) oral NMV/r was administered for 5 days to participants aged at least 6 years weighing at least 40 kg (Cohort 1) or 20 to <40 kg (Cohort 2). Day 1 and 5 sparse PK samples were incorporated into a previously developed population PK model to simulate exposure. Efficacy was extrapolated from adults by matching pediatric exposure to that in COVID-19-infected adults. Safety through Day 34 and supportive efficacy endpoints (hospitalization/death, SARS-CoV-2 RNA concentration over time) were evaluated. Overall, 75 participants received at least 1 dose. Simulated exposure of NMV/r 300/100 mg BID for Cohort 1 and 150/100 mg BID for Cohort 2 indicated more than 90% of participants achieved minimum NMV concentrations above the 90% effective concentration after dose 1 and at steady state. NMV/r was safe and well tolerated. The most frequently reported adverse events (AEs) were diarrhea and headache (n = 3 [4%] participants each). No discontinuations because of treatment-related AEs occurred. No treatment-related serious AEs were reported. No COVID-19-related hospitalizations or all-cause deaths were reported. Robust reductions in SARS-CoV-2 RNA from baseline to the end of treatment were observed. In pediatric participants aged at least 6 years, NMV/r 300/100 mg BID (weighing ≥40 kg) and 150/100 mg BID (weighing 20-<40 kg) regimens achieved exposures similar to adults that were safe and had an antiviral effect.