Efficacy and Safety of Favipiravir, an Oral RNA-Dependent RNA Polymerase Inhibitor, in Mild-to-Moderate COVID-19: A Randomized, Comparative, Open-Label, Multicenter, Phase 3 Clinical Trial

Udwadia, Zarir F.; Singh, Pawan; Barkate, Hanmant; Patil, Saiprasad; Rangwala, Shabbir; Pendse, Amol; Kadam, Jatin; Wu, Wen; Caracta, Cynthia F.; Tandon, Monika

Objective To assess efficacy and safety of favipiravir in adults with mild-to-moderate COVID-19. Methods In this randomized, open-label, parallel-arm, multicenter, Phase 3 trial, adults (18-75 years) with RT-PCR-confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (Day 1: 1800 mg BID; Days 2-14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to cessation of viral shedding; time to clinical cure also was measured. Results From May 14-July 3, 2020, 150 patients were randomized to favipiravir (n = 75) or control (n = 75). Median time to cessation of viral shedding was 5 days (95% CI: 4 days, 7 days) versus 7 days (95% CI: 5 days, 8 days),P = 0.129, and median time to clinical cure was 3 days (95% CI: 3 days, 4 days) versus 5 days (95% CI: 4 days, 6 days), P = 0.030, for favipiravir and control, respectively. Adverse events were observed in 36% of favipiravir and 8% of control patients. One control patient died due to worsening disease. Conclusion Lack of statistical significance on the primary endpoint was confounded by limitations of the RT-PCR assay. Significant improvement in time to clinical cure suggests favipiravir may be beneficial in mild-to-moderate COVID-19.