Remdesivir (RDV), a potent nucleotide inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase, effectively reduces COVID-19 related hospitalization in outpatients at high risk for progression to severe disease. However, limited data exist on the safety profile of RDV in this population.
We conducted a phase 3 placebo-controlled study evaluating a 3-day regimen of RDV in non-hospitalized patients who are at risk for disease progression (age>60 years or underlying comorbid condition). Patients were randomly assigned 1:1 to receive intravenous RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo (PBO). The primary safety endpoint was the proportion of patients with treatment-emergent adverse events (AEs). AEs were evaluated through day 28 and lab abnormalities were evaluated through day 14.
562 patients were randomized and initiated treatment (279, RDV; 283, placebo). Baseline characteristics were balanced between groups. Thirty percent were ?60 years old and most common comorbidities were diabetes mellitus (62%), obesity (56%; median BMI, 30.7 kg/m2), and hypertension (48%). RDV was well tolerated with a similar rate of any AEs between groups (Table). Patients treated with RDV had fewer Grade ?3 and serious AEs (SAEs) compared to PBO, but had more study-drug related AEs, with the most common one being nausea (18 [6.5%] in RDV vs. 10 [3.5%] in PBO). Grade 3 or higher ALT elevation was reported in 1 (0.4%) RDV vs. 2 (0.7%) PBO treated patients. Median change from baseline in AST, ALT, and bilirubin was similar between groups (Table). Grade 3 or higher decrease in creatinine clearance (CrCl) occurred more often in RDV vs. to PBO treated patients (5.6% vs 1.9% respectively). Most decreases in creatinine clearance occurred within the normal serum creatinine range, occurred after completion of RDV therapy, and resolved on follow-up. Median changes in CrCl from baseline were similar between groups and no renal AEs were reported (Table). Incidence of cardiac-related AEs was similar between RDV and PBO groups. All bradycardia events occurred in the PBO group. No patient experienced a serious AE or drug discontinuation due to hypersensitivity.
Treatment with RDV was safe and well tolerated in non-hospitalized patients with risk factors for COVID-19 disease progression. Patients in the RDV group had similar type, incidence, and severity of AEs and lab abnormalities as those receiving PBO.