LB1. Remdesivir for the Treatment of High-Risk Non-Hospitalized Individuals With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background. Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS‐CoV‐2 RNA‐dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID‐19. This Phase 3 (GS‐US‐540‐9012) double‐blind, placebo‐controlled study compared the efficacy and safety of 3 days of RDV to standard of care in non‐hospitalized, high‐risk participants with confirmed COVID‐19. Methods. Participants were randomly assigned 1:1 to receive intravenous (IV) RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo. The primary efficacy endpoint was composite COVID‐19 hospitalization or all‐cause death by day 28 and compared using Cox proportional hazards model with baseline stratification factors as covariates. The primary safety endpoint was proportion of participants with treatment‐emergent adverse events. Study enrollment was terminated early for administrative reasons in light of the evolving pandemic. Results. 562 patients underwent randomization and started their assigned treatment (279, RDV; 283, placebo). Baseline demographics and characteristics were balanced across arms. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were ≥ 60 years old. The most common comorbidities were diabetes mellitus (62%), obesity (56%; median BMI, 30.7), and hypertension (48%). Median baseline SARS‐CoV‐2 RNA nasopharyngeal viral load was 6.2 log10 copies/mL. Treatment with RDV significantly reduced COVID‐19 hospitalization or all‐cause death by day 28 (HR, 0.13; 95% CI, 0.03 ‐ 0.59; p = 0.008; Table 1) compared to placebo. Participants receiving RDV also had significantly lower risk for COVID‐19‐related medically attended visits or all‐cause death by day 28 compared to placebo (HR, 0.19; 95% CI, 0.07 ‐ 0.56; p = 0.002; Table 1). No deaths occurred in either arm by day 28. There was no difference between arms in time‐weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms (Table 1); the most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%). Conclusion. A 3‐day course of IV RDV was safe, well tolerated and highly effective at preventing COVID‐19 related hospitalization or death in high‐risk non‐hospitalized COVID‐19 patients.