A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19
J D Lundgren, B Grund, C E Barkaus- Kas, T L Holland, R L Gottlieb, U Sand- Kovsky, S M Brown, K U Knowlton, W H Self, D C Files, M K Jain, T Benfield, M E Bowdish, B G Leshnower, J V Bak- Er, J.-U Jensen, E M Gardner, A A Ginde, E S Harris, I S Johansen, N Markowitz, M A Matthay, L Østergaard, C C Chang, V J Davey, A Goodman, E S Higgs, D D Murray, T A Murray, R Paredes, M K B Parmar, A N Phillips, C Reilly, S Sharma, R L Dewar, M Teitelbaum, D Wentworth, H Cao, P Klekotka, A G Babiker, A C Gelijns, V L Kan, M N Polizzotto, B T Thompson, H C Lane, J D Neaton, / Tico Ly-Cov555, Study Group
New England Journal of Medicine, doi:10.1056/nejmoa2033130
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.
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