Lumicitabine, an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus (RSV) infection: Safety, efficacy, and pharmacokinetic results

• DOI: 10.1371/journal.pone.0288271
• Publication Date: 2023-07-19T18:45:16Z
• Authors: Abbie Oey; Matthew McClure; Julian A. Symons; Sushmita Chanda; John Fry; Patrick F. Smith; Kathia Luciani; Michael Fayon; Kulkanya Chokepha...; Rattapon Uppala; Jolanta Bernatoniene; Kenji Furuno; Thorsten Stanley; Dymphy Huntjens; James Witek
• Keywords: Pharmacodynamics; Pneumovirinae

Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for treatment RSV. The phase 1b 2b studies reported here assessed safety, pharmacokinetics, pharmacodynamics lumicitabine in infants/neonates hospitalized with In study, infants (≥1 to ≤12 months) neonates (<28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance [MD] lumicitabine, placebo [3:1]). infants/children (28 days ≤36 months old) 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily (1:1:1) 5 days. Safety, efficacy parameters were over 28 Lumicitabine associated dose-related increase incidence severity reversible neutropenia. Plasma levels ALS-008112, active analog, dose-proportional comparable mean exposure at highest both studies. There no significant differences between groups reducing viral load, time non-detectability, symptom resolution. No emergent resistance-associated substitutions observed RSV L-gene positions interest. summary, neutropenia failed demonstrate antiviral activity RSV-infected infants. This contrasts findings previous RSV-A adult challenge study where noted, without Trial registration ClinicalTrials.gov Identifier: NCT02202356 (phase 1b); NCT03333317 2b).