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

Brian O'Neil, Michael G Ison, Marie Charlotte Hallouin-Bernard, Anna C Nilsson, Antoni Torres, John M Wilburn, Wilbert van Duijnhoven, Ilse Van Dromme, David Anderson, Sofie Deleu, Teddy Kosoglou, Johan Vingerhoets, Stefaan Rossenu, Lorant Leopold, Brian O'Neil, Michael G Ison, Marie Charlotte Hallouin-Bernard, Anna C Nilsson, Antoni Torres, John M Wilburn, Wilbert van Duijnhoven, Ilse Van Dromme, David Anderson, Sofie Deleu, Teddy Kosoglou, Johan Vingerhoets, Stefaan Rossenu, Lorant Leopold

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.

Conflict of interest statement

Potential conflicts of interest . B. O’N. reports personal fees from Seqirus. M. G. I. reports personal fees from Celltrion, Genentech/Roche, GlaxoSmithKlein, Janssen, Seqirus, Shionogi, Viracor Eurofins, and VirBio; grants from Emergent BioSolutions, Genentech/Roche, and Janssen; payments to Northwestern University by AiCuris, Chimerix, Gilead, and Shire for research; and he was a nonpaid consultant for GlaxoSmithKlein, Romark, and Vertex. A. C. N. reports payments to Skåne University Hospital by Janssen. W. v. D., I. V. D., D. A., S. D., T. K., J. V., S. R., and L. L. are employees of Johnson & Johnson and may be stock holders. All other authors report no potential conflicts.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Study design schematic. Abbreviations: B, baseline; D, day.
Figure 2.
Figure 2.
Mean (SD) plasma concentration-time profiles for pimodivir after administration of pimodivir (600 mg, twice daily) plus oseltamivir (75mg, twice daily) in all patients.
Figure 3.
Figure 3.
Time to viral negativity determined by viral culture in patients treated with pimodivir plus oseltamivir compared with placebo plus oseltamivir. Abbreviations: AFT, accelerated failure time; CI, confidence interval.
Figure 4.
Figure 4.
Changes in patient status determined by the Hospital Recovery Scale in patients who started treatment within ≤72 hours (n = 36) or ≤96 hours (n = 55) after onset of influenza symptoms. Abbreviations: BL, baseline; ICU, intensive care unit; ECMO, extra corporeal membrane oxygenation.

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Source: PubMed

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