Pixavir Marboxil

Objective: To evaluate the antiviral effect, clinical efficacy, safety and tolerability of pixavir marboxil in adult patients with acute, uncomplicated influenza. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase Ⅱ clinical trial. Eligible participants were adults aged 18 to 64 years with acute, uncomplicated influenza, presenting within 48 hours of symptom onset with an axillary temperature ≥38.0 ℃ and ≥1 moderate-to-severe influenza symptom, who were neither severely ill nor at high risk for severe disease. Exclusion criteria included known hypersensitivity and recent antiviral use or vaccination. Participants were centrally randomized (1∶1∶1∶1) to oral pixavir marboxil (40 mg, 80 mg, or 40+40 mg) or placebo. Randomization was stratified by body weight (<80 kg vs.≥80 kg) and baseline influenza symptom score (<12 points vs.≥12 points). Rescue medications were permitted as clinically indicated during follow-up. The primary endpoint was the time to influenza virus RNA negativity by RT-PCR (time from first dose to the first RNA measurement below the lower limit of detection). Secondary endpoints included the time to relief of all influenza symptoms (severity scores of 0 or 1 for all 7 symptoms, sustained for ≥21.5 hours), time to cessation of infectious viral shedding by virus titer, time to resolution of fever, time to recovery to pre-influenza health status, changes from baseline in EQ-5D-5L scores, and the incidence of adverse events. Statistical analyses were performed using SAS 9.4. Efficacy was analyzed in the intention-to-treat infected (ITTI) and intention-to-treat (ITT) populations. Time-to-event data, including the primary endpoint, were estimated using the Kaplan-Meier method and compared between groups using the stratified Peto-Prentice generalized Wilcoxon test. Categorical data were analyzed using the Fisher's exact test or the Mantel-Haenszel test. Results: A total of 202 patients with influenza B were enrolled. In the ITTI population (107 cases), the median time to influenza virus RNA negativity was 28.2 h (95%CI: 19.73-43.88) in the 80 mg group, 35.5 h (95%CI: 23.43-45.05) in the 40 mg+40 mg group, and 42.4 h (95%CI: 22.60-57.53) in the 40 mg group, compared with 48.1 h (95%CI: 23.25-83.67) in the placebo group; between-group differences were not statistically significant (all P>0.05). The median times to cessation of infectious viral shedding by virus titer (TCID50) for the pixavir marboxil were [80 mg: 19.5 h (95%CI: 15.17-22.80); 40 mg: 22.6 h (95%CI: 14.72-44.85); 40 mg+40 mg: 23.1 h (95%CI: 18.63-26.98)] were versus the 45.8 h (95%CI: 20.20-68.57) in the placebo group; only the 80 mg group reached a statistically significant difference (P=0.027). In the ITT population (200 cases), pixavir marboxil 40 mg significantly shortened the median time to relief of all influenza symptoms compared to the placebo group [37.7 h (95%CI: 22.23-49.33) vs. 68.2 h (95%CI: 47.70-97.17), P=0.009], whereas the 80 mg group showed only a non-significant trend toward shortening 45.8 h [(95%CI: 34.50-62.67) vs. 68.2 h]. The median time to resolution of fever was significantly reduced in both the 40 mg [24.1 h (95%CI: 19.40-30.97)] and 80 mg [22.9 h (95%CI: 19.48-27.00)] groups compared with placebo [44.0 h (95%CI: 34.67-50.85)], with reductions of 19.9 h and 21.1 h, respectively (both P<0.001). The median time to recovery to pre-influenza health status was significantly shortened in the 80 mg [127.7 h (95%CI: 99.65-168.77)] and 40 mg [152.1 h (95%CI: 105.55-171.83)] groups compared with placebo [198.1 h (95%CI: 167.10-210.52)], with reductions of 70.4 h and 46.0 h, respectively (both P<0.05). The incidence of adverse events was comparable across groups: 13.5% (40 mg), 18.0% (80 mg), 20.4% (40 mg+40 mg), and 20.4% (placebo). No baseline or treatment-emergent resistance mutations were detected. Conclusion: Single-dose pixavir marboxil regimens demonstrated potential benefits in improving infectivity-related virologic measures and alleviating clinical symptoms in adults with uncomplicated influenza, with favorable overall tolerability. These findings provide a basis for subsequent confirmatory clinical trials.