For a study, researchers sought to assess the safety and effect of sotrovimab in preventing the development of mild to moderate COVID-19 disease to severe illness. From August 27, 2020, to March 11, 2021, 1,057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least one risk factor for progression were enrolled in a randomized clinical trial at 57 sites in Brazil, Canada, Peru, Spain, and the United States; follow-up data were collected through April 8, 2021. Patients were randomly assigned (1:1) to receive an intravenous infusion of 500 mg sotrovimab (n=528) or placebo (n=529). The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchical order, including a composite of all-cause ED visits, hospitalization of any duration for acute illness management or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen.
At the predetermined interim analysis, enrollment was halted early for effectiveness. The median period of follow-up for sotrovimab was 103 days and 102 days for placebo among 1,057 patients randomized (median age, 53 [IQR, 42-62], 20% were 65 years of age, and 65% were Latinx). Sotrovimab (6/528 [1%]) substantially decreased all-cause hospitalization or mortality compared to placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, –4.53% [95% CI, –6.70% to –2.37%]; P<.001). Four of the five secondary outcomes were statistically significant in favor of sotrovimab, including decreased ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, –4.91% [95% CI, –7.50% to –2.32%]; P<.001). and development to severe or critical respiratory COVID-19 (7/528 [1%] vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, –3.97% [95% CI, –6.11% to –1.82%]; P =.002). Adverse events were few and equal across treatment groups (22% for sotrovimab versus 23% for placebo); the most prevalent occurrences were diarrhea with sotrovimab (n=8; 2%), and COVID-19 pneumonia with placebo (n = 22; 4%).
A single intravenous dose of sotrovimab, compared to placebo, significantly decreased the probability of a composite endpoint of all-cause hospitalization or mortality in nonhospitalized patients with mild to severe COVID-19 and at risk of disease progression through day 29. The findings indicate sotrovimab as a therapy option for nonhospitalized, high-risk individuals with mild to moderate COVID-19, while effectiveness against SARS-CoV-2 variations discovered since the study’s completion was uncertain.