Nirmatrelvir/Ritonavir for the Treatment of COVID-19 in Children Aged 6 Years and Older
Jacqueline Gerhart, Heidi Leister-Tebbe, Phylinda L. S. Chan, Grace A. McComsey, William Carey, Haihong Shi, Jean Yan, Joanne Leaney, Namita Singh, Mary Lynn Baniecki, Shunjie Guan, Wayne Wisemandle, Ravi Shankar P. Singh, Jennifer HammondOBJECTIVES
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.