Remdesivir for COVID-19 in Hospitalized Children: A Phase 2/3 Study

• Published in: Pediatrics (Evanston) Vol. 153; no. 3
• Main Authors: Ahmed, Amina, Munoz, Flor M, Muller, William J, Agwu, Allison, Kimberlin, David W, Galli, Luisa, Deville, Jaime G, Sue, Paul K, Mendez-Echevarria, Ana, Humeniuk, Rita, Guo, Susan, Rodriguez, Lauren, Han, Dong, Hedskog, Charlotte, Maxwell, Heather, Palaparthy, Ramesh, Kersey, Kathryn, Rojo, Pablo
• Format: Journal Article
• Language: English
• Published: United States 01.03.2024
• Subjects: Adenosine Monophosphate - analogs & derivatives; Adult; Alanine - analogs & derivatives; Child; Child, Hospitalized; COVID-19; COVID-19 Drug Treatment; Humans; Infant; Pyrroles; SARS-CoV-2; Transaminases
• ISSN: 1098-4275
• DOI: 10.1542/peds.2023-063775

Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population-pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1-10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUCτ, Cmax, and Cτ) were largely overlapping but modestly increased (remdesivir, 33%-129%; GS-704277, 37%-124%; GS-441524, 0%-60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.