BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19.
METHODS: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5.
RESULTS: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47).
CONCLUSIONS: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.).
Bibliographical noteFunding Information:
Supported by the U.S. Operation Warp Speed program; the National Institute of Allergy and Infectious Diseases and Leidos Biomedical Research for the INSIGHT Network; the National Heart, Lung, and Blood Institute and the Research Triangle Institute for the PETAL (Prevention and Early Treatment of Acute Lung Injury) Network and the Cardiothoracic Surgical Trials Network; and the U.S. Department of Veterans Affairs and grants from the governments of Denmark (no. 126 from the National Research Foundation), Australia (from the National Health and Medical Research Council), and the United Kingdom (MRC_UU_12023/23 from the Medical Research Council). Trial medications were donated by Gilead Sciences and Eli Lilly.
Copyright © 2020 Massachusetts Medical Society.
- Adenosine Monophosphate/analogs & derivatives
- Alanine/analogs & derivatives
- Antibodies, Monoclonal, Humanized/adverse effects
- Antibodies, Neutralizing/adverse effects
- Antiviral Agents/adverse effects
- COVID-19/drug therapy
- Double-Blind Method
- Drug Therapy, Combination
- Glucocorticoids/therapeutic use
- Intention to Treat Analysis
- Middle Aged
- Treatment Failure
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Randomized Controlled Trial
- Multicenter Study
- Journal Article
- Research Support, N.I.H., Extramural