Efficacy and Safety of WXSH0208 Tablets in Treatment of Acute Uncomplicated Influenza Infection in Adults: A Multicenter Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Abstract

Background: WXSH0208 is a selective inhibitor of influenza RNA polymerase subunit, demonstrating antiviral activity in preclinical studies against influenza A and B virus infections. The purpose of this study was to investigate the efficacy and safety of WXSH0208 in adult outpatients with uncomplicated influenza.

Methods: We conducted a multicenter phase 2 trial based on a randomized, double-blind, placebo-controlled design at 23 research centers in China from November 2023 to March 2024. Participants were randomized 1:1:1:1 to receive one of the following treatments within 48 hours of symptom onset: WXSH0208 10 mg once daily for 5 days, 20 mg once daily for 5 days, 30 mg once daily for 3 days, or placebo. The primary outcome was the time to negative detection of viral load by reverse transcriptase quantitative polymerase chain reaction in the intention-to-treat infected population.

Results: Of 240 randomized patients, 209 were included in the intention-to-treat infected analysis. The median time to negative detection of viral load was 49.3 hours in the WXSH0208 10 mg group, 48.0 hours in the 20 mg group, and 48.2 hours in the 30 mg group, as compared with 95.6 hours in the placebo group (P < .001). Time to alleviation of influenza symptoms was comparable among all groups. Treatment-emergent adverse events were reported in 48.3% to 51.7% of WXSH0208 recipients and 58.3% of placebo recipients, with most being mild or moderate in severity.

Conclusions: WXSH0208 showed no evident safety concerns and was superior to placebo in reducing viral load in adult outpatients with uncomplicated influenza. Clinical Trials Registration. CTR20233250 (www.chinadrugtrials.org.cn).