Lumicitabine, an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus

Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumi...

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Published in:PloS one 2023-07, Vol.18 (7), p.e0288271
Main Authors: Oey, Abbie, McClure, Matthew, Symons, Julian A, Chanda, Sushmita, Fry, John, Smith, Patrick F, Luciani, Kathia, Fayon, Michael, Chokephaibulkit, Kulkanya, Uppala, Rattapon, Bernatoniene, Jolanta, Furuno, Kenji, Stanley, Thorsten, Huntjens, Dymphy, Witek, James
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Language:English
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Care and treatment
Complications and side effects
Health aspects
Infants (Newborn)
Nucleosides
Patient outcomes
Respiratory syncytial virus
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container_issue 7
container_start_page e0288271
container_title PloS one
container_volume 18
creator Oey, Abbie
McClure, Matthew
Symons, Julian A
Chanda, Sushmita
Fry, John
Smith, Patrick F
Luciani, Kathia
Fayon, Michael
Chokephaibulkit, Kulkanya
Uppala, Rattapon
Bernatoniene, Jolanta
Furuno, Kenji
Stanley, Thorsten
Huntjens, Dymphy
Witek, James
description Respiratory syncytial virus (RSV) infection is the leading cause of infant hospitalizations and mortality. Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants ([greater than or equal to]1 to [less than or equal to]12 months) and neonates (
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Lumicitabine, an oral nucleoside analog was studied for the treatment of RSV. The phase 1b and phase 2b studies reported here assessed the safety, pharmacokinetics, and pharmacodynamics of lumicitabine in infants/neonates hospitalized with RSV. In the phase 1b study, infants ([greater than or equal to]1 to [less than or equal to]12 months) and neonates (&lt;28 days) received a single-ascending or multiple-ascending doses (single loading dose [LD] then 9 maintenance doses [MD] of lumicitabine, or placebo [3:1]). In the phase 2b study, infants/children (28 days to [less than or equal to]36 months old) received lumicitabine 40/20 mg/kg, 60/40 mg/kg LD/MD twice-daily or placebo (1:1:1) for 5 days. Safety, pharmacokinetics, and efficacy parameters were assessed over 28 days. Lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia. Plasma levels of ALS-008112, the active nucleoside analog, were dose-proportional with comparable mean exposure levels at the highest doses in both studies. There were no significant differences between the lumicitabine groups and placebo in reducing viral load, time to viral non-detectability, and symptom resolution. No emergent resistance-associated substitutions were observed at the RSV L-gene positions of interest. In summary, lumicitabine was associated with a dose-related increase in the incidence and severity of reversible neutropenia and failed to demonstrate antiviral activity in RSV-infected hospitalized infants. 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subjects Care and treatment
Complications and side effects
Health aspects
Infants (Newborn)
Nucleosides
Patient outcomes
Respiratory syncytial virus
title Lumicitabine, an orally administered nucleoside analog, in infants hospitalized with respiratory syncytial virus
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