Introduction
RSV infection, acute infections, Respiratory Syncytial Virus, PD, viral infections
ACUTE INFECTIONS, RSV INFECTION, VIRUS, VIRAL INFECTION
Respiratory Syncytial Virus (RSV), a ribonucleic acid (RNA) virus belonging to the The management of RSV infection in children is mainly supportive; the current treatment of RSV is primarily symptomatic, including supplemental oxygen therapy, hydration, and supplemental nutrition [Nucleoside analogs have been developed as direct-acting agents against multiple viral infections. However, these have not yet been successfully developed against acute infections caused by RSV [In a phase 1 study in healthy adults, lumicitabine was rapidly converted to ALS-008112 following a single oral fasted dose ranging from 40 mg to 750 mg, with measurable plasma concentrations detected within an approximate period of 15–30 minutes. Low levels of the drug plasma concentrations were detected within 6 hours post-dose. Multiple doses of lumicitabine, including two loading doses (LD; 375 mg and 750 mg) on day 1, followed by the twice-daily administration of maintenance doses (MD; 125 mg, 250 mg, and 500 mg) from days 2 to 5, resulted in no accumulation of ALS-008112 or its uridine metabolite (ALS-008144). The steady-state minimum observed concentration (CIn a phase 1 RSV-A human challenge study, lumicitabine inhibited viral replication, reduced viral load, and enhanced viral clearance in healthy volunteers [Here, we present the results of ALS-8176-503 (Study 1; NCT02202356), a phase 1b study conducted to evaluate the safety, PK, PD (absolute viral load and effect of exposure on viral kinetics), and the emergence of viral resistance after single- and multiple-ascending doses of lumicitabine in hospitalized infants and neonates with RSV infection. Additionally, we report limited results of 64041575RSV2004 (Study 2; NCT03333317), a related phase 2b study of lumicitabine in a small number of hospitalized infants and children with RSV, terminated early by the sponsor.