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- Title
Safety and Antiviral Effects of Nebulized PC786 in a Respiratory Syncytial Virus Challenge Study.
- Authors
DeVincenzo, John; Cass, Lindsey; Murray, Alison; Woodward, Kathy; Meals, Elizabeth; Coates, Matthew; Daly, Leah; Wheeler, Vicky; Mori, Julie; Brindley, Charlie; Davis, Amanda; McCurdy, Meabh; Ito, Kazuhiro; Murray, Bryan; Strong, Pete; Rapeport, Garth
- Abstract
<bold>Background: </bold>PC786 is a nebulized nonnucleoside respiratory syncytial virus (RSV) polymerase inhibitor designed to treat RSV, which replicates in the superficial layer of epithelial cells lining the airways.<bold>Methods: </bold>Fifty-six healthy volunteers inoculated with RSV-A (Memphis 37b) were randomly dosed with either nebulized PC786 (5 mg) or placebo, twice daily for 5 days, from either 12 hours after confirmation of RSV infection or 6 days after virus inoculation. Viral load (VL), disease severity, pharmacokinetics, and safety were assessed until discharge. RSV infection was confirmed by reverse-transcription quantitative polymerase chain reaction with any positive value (intention-to-treat infected [ITT-I] population) or RSV RNA ≥1 log10 plaque-forming unit equivalents (PFUe)/mL (specific intention-to-treat infection [ITT-IS] population) in nasal wash samples.<bold>Results: </bold>In the ITT-I population, the mean VL area under the curve (AUC) was lower in the PC786 group than the placebo group (274.1 vs 406.6 log10 PFUe/mL × hour; P = .0359). PC786 showed a trend toward reduction of symptom score and mucous weight. In ITT-IS (post hoc analysis), the latter was statistically significant as well as VL AUC (P = .0126). PC786 showed an early time to maximum plasma concentration, limited systemic exposure, and long half-life and consequently a 2-fold accumulation over the 5-day dosing period. PC786 was well tolerated.<bold>Conclusions: </bold>Nebulized PC786 demonstrated a significant antiviral effect against RSV, warranting further clinical study.<bold>Clinical Trials Registration: </bold>ClinicalTrials.gov: NCT03382431; EudraCT: 2017-002563-18.
- Publication
Journal of Infectious Diseases, 2022, Vol 225, Issue 12, p2087
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jiaa716