Randomized Controlled Trial
Study population and setting
326 patients were randomized 1:1 to receive the antibody LY-CoV555 (developed by Eli Lilly) or placebo. Patients included in this study were adults hospitalized with SARS-CoV-2 infection, and no end-organ failure (i.e., vasopressor therapy, new renal-replacement therapy, invasive mechanical ventilation, extracorporeal membrane oxygenation, or mechanical circulatory support) or certain extrapulmonary complications. Patients who received SARS-CoV-2 intravenous immune globulin, convalescent plasma therapy, or another neutralizing monoclonal antibody against SARS-CoV-2 were excluded from this study. All patients were hospitalized and received supportive care and remdesivir, as well as supplemental oxygen and glucocorticoids when indicated. Patients were enrolled at 31 trials sites across the United States, Denmark and Singapore. LY-CoV555 (7000 mg dose) or placebo was administered once intravenously over a 1-hour period. A modified intention-to-treat analysis was done, including all the patients who received all or part of the LY-CoV555 or placebo infusion. The primary efficacy outcome was 90-day sustained recovery (time-to-event analysis). In addition, on day 5 since the onset of symptoms, patients were classified on a seven-level ordinal scale regarding pulmonary and pulmonary-plus outcomes. The primary safety outcome was a composite measure of death and adverse events through day 5 since the onset of symptoms.
Summary of Main Findings
Enrollment into this trial was stopped following an interim futility assessment of 314 patients. Of the 314, patients 163 patients received LY-CoV555 infusion and 151 patients received placebo. The median time from symptom onset to enrollment was 7 days (interquartile range [IQR]: 5-9 days) and the median duration of follow-up was 31 days. By chance, individuals in the LY-CoV555 infusion arm were somewhat more likely to be at risk of severe disease progression compared to patients in the placebo arm. At day 5 since the onset of symptoms, 50% of patients receiving LY-CoV555 and 54% receiving placebo were in one of the two best categories of the pulmonary outcome (OR 0.85; 95% CI, 0.56 to 1.29). There was no statistically significant difference in the rate of sustained recovery between groups, with a rate ratio of 1.06 (95% CI, 0.77 to 1.47) comparing those receiving LY-CoV555 to placebo Regarding the composite safety outcome, there also was no statistically signicant difference between groups (19% of patients in the LY-CoV555 group with the outcome vs. 14% in the placebo group; OR 1.56; 95% CI, 0.78 to 3.10), although more adverse advents were observed in the LY-CoV555 arm. In adjusted analyses for baseline co-variates and in pre-specified sub-group analyses, LY-CoV555 showed no evidence of benefit, including among those treated earlier in symptom onset.
This was a randomized double-blinded controlled trial. Primary and secondary outcomes included safety, tolerability, and changes in clinical condition. Patients were recruited from sites across three different countries, and 53% of the participants were non-white. Several pregnant women were also included in this study.
Only one dose (7000 mg) of LY-CoV555 was evaluated; other studies have evaluated higher and lower doses of monoclonal antibodies. Study power was limited to evaluate differences in safety outcomes between study arms. In addition, all patients in the study population were hospitalized with no end-organ failure. Thus, findings may not be generalizable to non-hospitalized individuals with COVID-19 or to those with end-organ failure.
This randomized controlled trial provides preliminary evidence of a lack benefit of the intravenous infusion of the antibody LY-CoV555 (7000 mg) among patients hospitalized with COVID-19.
This review was posted on: 19 February 2021