Neutralizing Antibody in Outpatients with Covid-19 the Declaration of Helsinki and the ethical guide- lines of the Council for International Organiza- 1ƒ1 Patients …ere enrolled and assined tions of Medical Sciences. All the patients pro- to „ƒƒ m of ‡ˆ-CoV‰‰‰ monoterapy Interim Analysis vided written informed consent. Positive SARS-CoV-2 test ≤3 days 1ƒ„ Patients …ere enrolled and assined before infusion to 2†ƒƒ m of ‡ˆ-CoV‰‰‰ monoterapy Mild or moderate Covid-19 symptoms Outcomes Primary end point ane from The primary outcome was the change from baseline to day 11 ± days­ 1ƒ1 Patients …ere enrolled and assined in SARS-CoV-2 viral load baseline in the SARS-CoV-2 viral load at day 11 to „ƒƒƒ m of ‡ˆ-CoV‰‰‰ monoterapy Seondary end points inlude safety€ (±4 days) after positive results on testing. Data symptom severity€ ospitali‚ation€ 1 3 Patients …ere enrolled and assined and time points for viral learane regarding virologic features and symptoms were to plaebo collected up to day 29 in this trial. The viral load was measured by means of a nasopharyngeal swab, which was followed by quantitative reverse- Figure 1. Enrollment and Trial Design. transcriptase–polymerase-chain-reaction (RT-PCR) assay at a central laboratory. (Details regarding testing are provided in the Methods section in regarding these methods are provided in Section the Supplementary Appendix.) Key secondary out- 6.10 in the statistical analysis plan.) comes were safety assessments, symptom burden as reported by the patient on a questionnaire, Results and clinical outcomes. The major clinical out- come was defined as Covid-19–related in-patient Patients hospitalization, a visit to the emergency depart- From June 17 through August 21, 2020, a total ment, or death. No deaths were reported, and of 467 patients underwent randomization to re- since most emergency department visits resulted ceive either LY-CoV555 (317 patients) or placebo in hospital admissions, we refer to a composite of (150 patients), and the patients in the LY-CoV555 emergency department visits and in-patient hos- group were assigned to one of three dose sub- pitalizations simply as hospitalizations. This re- groups. Of the patients who had undergone port includes an analysis of the primary outcome randomization, 452 met the criteria for inclusion as well as safety and adverse-event data, informa- in the primary analysis (309 in the LY-CoV555 tion regarding symptoms, and clinical outcomes. group and 143 in the placebo group). LY-CoV555 was administered to these patients in doses of Statistical Analysis 700 mg (101 patients), 2800 mg (107 patients), or To determine the sample size, we used a dynamic 7000 mg (101 patients) (Fig. 1). The two trial model to simulate viral load over time in patients groups were well balanced regarding risk factors treated with LY-CoV555 or placebo. This simu- at the time of enrollment (Table 1). Nearly 70% lated population was used to estimate the statis- of the patients had at least one risk factor — an tical power and comparisons in the change from age of 65 years or older, a body-mass index baseline in viral load. (Details are provided in (BMI, the weight in kilograms divided by the Section 5.2 in the statistical analysis plan, which square of the height in meters) of 35 or more, or is included in the protocol document.) All the at least one relevant coexisting illness — for patients who had undergone randomization and severe Covid-19. After undergoing randomiza- who had received either LY-CoV555 or placebo tion, patients received an infusion of LY-CoV555 were included in the primary analysis if their or placebo within a median of 4 days after the viral-load measures were available both at base- onset of symptoms; at the time of randomiza- line and at least once after baseline. tion, more than 80% of the patients had only Treatment effects were compared with the mild symptoms. The observed mean PCR cycle use of two-sided tests with an alpha level of 0.05. threshold (Ct) value of 23.9 on the day of infu- Adjustments for multiple testing were not per- sion (equating to approximately 2.5 million RNA formed. Significance testing for the primary out- equivalents) matched expectations that a recently come was performed with the use of a repeated- diagnosed population would have a high viral measures analysis as a mixed model. (Details burden. The conversion from Ct value to viral load n engl j med nejm.org 3 The New England Journal of Medicine Downloaded from nejm.org on November 19, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved.