A neutralizing monoclonal antibody for hospitalized patients with Covid-19

ACTIV-3/TICO LY-CoV555 Study Group

doi:10.1056/NEJMoa2033130

A neutralizing monoclonal antibody for hospitalized patients with Covid-19

ACTIV-3/TICO LY-CoV555 Study Group

Research output: Contribution to journal › Article › peer-review

319 Scopus citations

Abstract

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.).

Original language	English (US)
Pages (from-to)	905-914
Number of pages	10
Journal	New England Journal of Medicine
Volume	384
Issue number	10
DOIs	https://doi.org/10.1056/NEJMoa2033130
State	Published - Mar 11 2021

Bibliographical note

Funding 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.

Publisher Copyright:
Copyright © 2020 Massachusetts Medical Society.

Keywords

Adenosine Monophosphate/analogs & derivatives
Adult
Aged
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
Female
Glucocorticoids/therapeutic use
Hospitalization
Humans
Intention to Treat Analysis
Male
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1056/NEJMoa2033130

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@article{7a4e3af517a74494a91126bed2feed0f,

title = "A neutralizing monoclonal antibody for hospitalized patients with Covid-19",

abstract = "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.).",

keywords = "Adenosine Monophosphate/analogs & derivatives, Adult, Aged, 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, Female, Glucocorticoids/therapeutic use, Hospitalization, Humans, Intention to Treat Analysis, Male, Middle Aged, Treatment Failure",

author = "{ACTIV-3/TICO LY-CoV555 Study Group} and Lundgren, {J. D.} and B. Grund and Barkauskas, {C. E.} and Holland, {T. L.} and Gottlieb, {R. L.} and U. Sandkovsky and Brown, {S. M.} and Knowlton, {K. U.} and Self, {W. H.} and Files, {D. C.} and Jain, {M. K.} and T. Benfield and Bowdish, {M. E.} and Leshnower, {B. G.} and Baker, {J. V.} and Jensen, {J. U.} and Gardner, {E. M.} and Ginde, {A. A.} and Harris, {E. S.} and Johansen, {I. S.} and N. Markowitz and Matthay, {M. A.} and L. {\O}stergaard and Chang, {C. C.} and Davey, {V. J.} and A. Goodman and Higgs, {E. S.} and Murray, {D. D.} and Murray, {T. A.} and R. Paredes and Parmar, {M. K.B.} and Phillips, {A. N.} and C. Reilly and S. Sharma and Dewar, {R. L.} and M. Teitelbaum and D. Wentworth and H. Cao and P. Klekotka and Babiker, {A. G.} and Gelijns, {A. C.} and Kan, {V. L.} and Polizzotto, {M. N.} and Thompson, {B. T.} and Lane, {H. C.} and Neaton, {J. D.}",

note = "Funding 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. Publisher Copyright: Copyright {\textcopyright} 2020 Massachusetts Medical Society.",

year = "2021",

month = mar,

day = "11",

doi = "10.1056/NEJMoa2033130",

language = "English (US)",

volume = "384",

pages = "905--914",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "10",

}

TY - JOUR

T1 - A neutralizing monoclonal antibody for hospitalized patients with Covid-19

AU - ACTIV-3/TICO LY-CoV555 Study Group

AU - Lundgren, J. D.

AU - Grund, B.

AU - Barkauskas, C. E.

AU - Holland, T. L.

AU - Gottlieb, R. L.

AU - Sandkovsky, U.

AU - Brown, S. M.

AU - Knowlton, K. U.

AU - Self, W. H.

AU - Files, D. C.

AU - Jain, M. K.

AU - Benfield, T.

AU - Bowdish, M. E.

AU - Leshnower, B. G.

AU - Baker, J. V.

AU - Jensen, J. U.

AU - Gardner, E. M.

AU - Ginde, A. A.

AU - Harris, E. S.

AU - Johansen, I. S.

AU - Markowitz, N.

AU - Matthay, M. A.

AU - Østergaard, L.

AU - Chang, C. C.

AU - Davey, V. J.

AU - Goodman, A.

AU - Higgs, E. S.

AU - Murray, D. D.

AU - Murray, T. A.

AU - Paredes, R.

AU - Parmar, M. K.B.

AU - Phillips, A. N.

AU - Reilly, C.

AU - Sharma, S.

AU - Dewar, R. L.

AU - Teitelbaum, M.

AU - Wentworth, D.

AU - Cao, H.

AU - Klekotka, P.

AU - Babiker, A. G.

AU - Gelijns, A. C.

AU - Kan, V. L.

AU - Polizzotto, M. N.

AU - Thompson, B. T.

AU - Lane, H. C.

AU - Neaton, J. D.

N1 - Funding 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. Publisher Copyright: Copyright © 2020 Massachusetts Medical Society.

PY - 2021/3/11

Y1 - 2021/3/11

N2 - 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.).

AB - 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.).

KW - Adenosine Monophosphate/analogs & derivatives

KW - Adult

KW - Aged

KW - Alanine/analogs & derivatives

KW - Antibodies, Monoclonal, Humanized/adverse effects

KW - Antibodies, Neutralizing/adverse effects

KW - Antiviral Agents/adverse effects

KW - COVID-19/drug therapy

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Glucocorticoids/therapeutic use

KW - Hospitalization

KW - Humans

KW - Intention to Treat Analysis

KW - Male

KW - Middle Aged

KW - Treatment Failure

UR - http://www.scopus.com/inward/record.url?scp=85099949020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85099949020&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa2033130

DO - 10.1056/NEJMoa2033130

M3 - Article

C2 - 33356051

AN - SCOPUS:85099949020

SN - 0028-4793

VL - 384

SP - 905

EP - 914

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 10

ER -

A neutralizing monoclonal antibody for hospitalized patients with Covid-19

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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