A Phase 2 Study of Pimodivir (JNJ-63623872) in Combination With Oseltamivir in Elderly and Nonelderly Adults Hospitalized With Influenza A Infection: OPAL Study

J Infect Dis. 2022 Aug 12;226(1):109-118. doi: 10.1093/infdis/jiaa376.

Abstract

Background: Both the elderly and individuals with comorbidities are at increased risk of developing influenza-related complications. Novel influenza antivirals are required, given limitations of current drugs (eg, resistance emergence and poor efficacy). Pimodivir is a first-in-class antiviral for influenza A under development for these patients.

Methods: Hospitalized patients with influenza A infection were randomized 2:1 to receive pimodivir 600 mg plus oseltamivir 75 mg or placebo plus oseltamivir 75 mg twice daily for 7 days in this phase 2b study. The primary objective was to compare pimodivir pharmacokinetics in elderly (aged 65-85 years) versus nonelderly adults (aged 18-64 years). Secondary end points included time to patient-reported symptom resolution.

Results: Pimodivir pharmacokinetic parameters in nonelderly and elderly patients were similar. Time to influenza symptom resolution was numerically shorter with pimodivir (72.45 hours) than placebo (94.15 hours). There was a lower incidence of influenza-related complications in the pimodivir group (7.9%) versus placebo group (15.6%). Treatment was generally well tolerated.

Conclusions: No apparent relationship was observed between pimodivir pharmacokinetics and age. Our data demonstrate the need for a larger study of pimodivir in addition to oseltamivir to test whether it results in a clinically significant decrease in time-to-influenza-symptom alleviation and/or the frequency of influenza complications.

Clinical trials registration: NCT02532283.

Keywords: clinical trial; duration of symptoms; elderly; hospitalized; influenza A virus; influenza complications; oseltamivir; pharmacokinetics; pimodivir; viral clearance.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents
  • Humans
  • Influenza, Human* / drug therapy
  • Middle Aged
  • Oseltamivir* / therapeutic use
  • Pyridines / therapeutic use
  • Pyrroles / pharmacokinetics
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Oseltamivir
  • pimodivir
  • Pyridines
  • Pyrroles

Associated data

  • ClinicalTrials.gov/NCT02532283