A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.
(Journal Article;Multicenter Study)
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.).
ACTIV-3/TICO LY-CoV555 Study Group, ; Lundgren, JD; Grund, B; Barkauskas, CE; Holland, TL; Gottlieb, RL; Sandkovsky, U; Brown, SM; Knowlton, KU; Self, WH; Files, DC; Jain, MK; Benfield, T; Bowdish, ME; Leshnower, BG; Baker, JV; Jensen, J-U; Gardner, EM; Ginde, AA; Harris, ES; Johansen, IS; Markowitz, N; Matthay, MA; Østergaard, L; Chang, CC; Davey, VJ; Goodman, A; Higgs, ES; Murray, DD; Murray, TA; Paredes, R; Parmar, MKB; Phillips, AN; Reilly, C; Sharma, S; Dewar, RL; Teitelbaum, M; Wentworth, D; Cao, H; Klekotka, P; Babiker, AG; Gelijns, AC; Kan, VL; Polizzotto, MN; Thompson, BT; Lane, HC; Neaton, JD
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