Efficacy and Safety of Pimodivir Combined With Standard of Care in Hospitalized and Nonhospitalized High-Risk Adolescents and Adults With Influenza A Infection

Abstract

Background: An unmet need exists for effective antivirals to treat patients hospitalized with influenza. The results of 2 phase 3 studies that evaluated the efficacy and safety of pimodivir in combination with investigator-chosen standard of care (SoC) treatment are presented.

Methods: Hospitalized patients (hospital study; NCT03376321) and high-risk outpatients (outpatient study; NCT03381196) with laboratory-confirmed influenza A infection were randomized 1:1 to 600 mg pimodivir twice daily + SoC or placebo twice daily + SoC for 5 days. For most patients, SoC included oseltamivir. Primary end points were Hospital Recovery Scale (HRS) at day 6 (hospital study) and median time to resolution (TTR) of influenza-related symptoms (outpatient study).

Results: Pimodivir + SoC (oseltamivir) treatment showed no clinical benefit over placebo + SoC on HRS at day 6 (common odds ratio, 0.943; 95% confidence interval [CI], .609-1.462; P = .397; hospital study). A shorter median TTR of 7 symptoms was estimated with pimodivir + SoC versus placebo (92.6 hours; 95% CI, 77.6-104.2 vs 105.1 hours; 95% CI, 92.7-128.6; P = .0216; outpatient study).

Conclusions: Pimodivir + SoC showed no additional clinical benefit versus SoC treatment alone in hospitalized patients. Pimodivir + SoC demonstrated shorter TTR of influenza symptoms versus placebo + SoC in high-risk outpatients.

Clinical trial registration: NCT03376321 and NCT03381196.

Keywords: Hospital Recovery Scale; hospitalized patients; influenza A; ordinal endpoint; respiratory viral infection.

Figure 1.

HRS on day 6 in the hospital study in (A) the ITT-i set (n = 318) and (B) the OST ITT-i set (n = 296). Abbreviations: HRS, Hospital Recovery Scale; ICU, intensive care unit; ITT-i, intent-to-treat infected; OST, oseltamivir; OST ITT-i, subset from ITT-i set whose SoC treatment contained OST; SoC, standard of care.

Figure 2.

TTR of 7 primary influenza-related symptoms in the outpatient study in the (A) ITT-i set (n = 446) and (B) OST ITT-i set (n = 381). The estimated curves (AFT model, smooth lines) and the Kaplan-Meier curves (stepwise lines) of the TTR of the 7 primary influenza-related symptoms are shown. Abbreviations: ITT-i, intent-to-treat infected; OST, oseltamivir; OST ITT-i, subset from ITT-i set whose SoC treatment contained OST; SoC, standard of care; TTR, time to resolution.

Figure 3.

TTR of 7 primary influenza-related symptoms in the outpatient study in the ITT-i set in participants with (A) symptom onset ≤48 hours and (B) baseline SoC including influenza antiviral treatment. Abbreviations: ITT-i, intent-to-treat infected; SoC, standard of care; TTR, time to resolution.

Figure 4.

Viral load analyses in the hospital study, assessed by (A) mean log₁₀ viral load over time (as measured by qRT-PCR) and (B) mean log₁₀ viral titer over time (as measured by viral culture) in the ITT-i set. Abbreviations: ITT-i, intent-to-treat infected; qRT-PCR, quantitative reverse transcription polymerase chain reaction; SE, standard error; SoC, standard of care.

Figure 5.

Viral load analyses in the outpatient study, assessed by (A) mean log₁₀ viral load over time (as measured by qRT-PCR) and (B) mean log₁₀ viral titer over time (as measured by viral culture) in the ITT-i set. Abbreviations: ITT-i, intent-to-treat infected; qRT-PCR, quantitative reverse transcription polymerase chain reaction; SE, standard error; SoC, standard of care.