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Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial

IMPORTANCE: The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and...

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Autores principales: Portal-Celhay, Cynthia, Forleo-Neto, Eduardo, Eagan, Will, Musser, Bret J., Davis, John D., Turner, Kenneth C., Norton, Thomas, Hooper, Andrea T., Hamilton, Jennifer D., Pan, Cynthia, Mahmood, Adnan, Baum, Alina, Kyratsous, Christos A., Kim, Yunji, Parrino, Janie, Kampman, Wendy, Roque-Guerrero, Lilia, Stoici, Roxana, Fatakia, Adil, Soo, Yuhwen, Geba, Gregory P., Kowal, Bari, DiCioccio, A. Thomas, Stahl, Neil, Lipsich, Leah, Braunstein, Ned, Herman, Gary A., Yancopoulos, George D., Weinreich, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379747/
https://www.ncbi.nlm.nih.gov/pubmed/35969402
http://dx.doi.org/10.1001/jamanetworkopen.2022.25411
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author Portal-Celhay, Cynthia
Forleo-Neto, Eduardo
Eagan, Will
Musser, Bret J.
Davis, John D.
Turner, Kenneth C.
Norton, Thomas
Hooper, Andrea T.
Hamilton, Jennifer D.
Pan, Cynthia
Mahmood, Adnan
Baum, Alina
Kyratsous, Christos A.
Kim, Yunji
Parrino, Janie
Kampman, Wendy
Roque-Guerrero, Lilia
Stoici, Roxana
Fatakia, Adil
Soo, Yuhwen
Geba, Gregory P.
Kowal, Bari
DiCioccio, A. Thomas
Stahl, Neil
Lipsich, Leah
Braunstein, Ned
Herman, Gary A.
Yancopoulos, George D.
Weinreich, David M.
author_facet Portal-Celhay, Cynthia
Forleo-Neto, Eduardo
Eagan, Will
Musser, Bret J.
Davis, John D.
Turner, Kenneth C.
Norton, Thomas
Hooper, Andrea T.
Hamilton, Jennifer D.
Pan, Cynthia
Mahmood, Adnan
Baum, Alina
Kyratsous, Christos A.
Kim, Yunji
Parrino, Janie
Kampman, Wendy
Roque-Guerrero, Lilia
Stoici, Roxana
Fatakia, Adil
Soo, Yuhwen
Geba, Gregory P.
Kowal, Bari
DiCioccio, A. Thomas
Stahl, Neil
Lipsich, Leah
Braunstein, Ned
Herman, Gary A.
Yancopoulos, George D.
Weinreich, David M.
author_sort Portal-Celhay, Cynthia
collection PubMed
description IMPORTANCE: The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. OBJECTIVE: To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021. INTERVENTIONS: Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline. RESULTS: Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanic or Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from –0.56 (95% CI; –0.89 to –0.24) log(10) copies/mL for the 1200-mg IV dose to –0.71 (95% CI, –1.05 to –0.38) log(10) copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusion-related or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial including outpatients with asymptomatic and low-risk symptomatic SARS-CoV-2, all IV and SC doses of casirivimab and imdevimab comparably reduced viral load. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04666441
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spelling pubmed-93797472022-08-26 Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial Portal-Celhay, Cynthia Forleo-Neto, Eduardo Eagan, Will Musser, Bret J. Davis, John D. Turner, Kenneth C. Norton, Thomas Hooper, Andrea T. Hamilton, Jennifer D. Pan, Cynthia Mahmood, Adnan Baum, Alina Kyratsous, Christos A. Kim, Yunji Parrino, Janie Kampman, Wendy Roque-Guerrero, Lilia Stoici, Roxana Fatakia, Adil Soo, Yuhwen Geba, Gregory P. Kowal, Bari DiCioccio, A. Thomas Stahl, Neil Lipsich, Leah Braunstein, Ned Herman, Gary A. Yancopoulos, George D. Weinreich, David M. JAMA Netw Open Original Investigation IMPORTANCE: The monoclonal antibody combination of casirivimab and imdevimab reduced viral load, hospitalization, or death when administered as a 1200-mg or greater intravenous (IV) dose in a phase 3 COVID-19 outpatient study. Subcutaneous (SC) and/or lower IV doses should increase accessibility and/or drug supplies for patients. OBJECTIVE: To assess the virologic efficacy of casirivimab and imdevimab across different IV and SC doses compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study included outpatients with SARS-CoV-2 infection at 47 sites across the United States. Participants could be symptomatic or asymptomatic; symptomatic patients with risk factors for severe COVID-19 were excluded. Data were collected from December 15, 2020, to March 4, 2021. INTERVENTIONS: Patients were randomized to a single IV dose (523 patients) of casirivimab and imdevimab at 300, 600, 1200, or 2400 mg or placebo; or a single SC dose (292 patients) of casirivimab and imdevimab at 600 or 1200 mg or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was the time-weighted average daily change from baseline (TWACB) in viral load from day 1 (baseline) through day 7 in patients seronegative for SARS-CoV-2 at baseline. RESULTS: Among 815 randomized participants, 507 (282 randomized to IV treatment, 148 randomized to SC treatment, and 77 randomized to placebo) were seronegative at baseline and included in the primary efficacy analysis. Participants randomized to IV had a mean (SD) age of 34.6 (9.6) years (160 [44.6%] men; 14 [3.9%] Black; 121 [33.7%] Hispanic or Latino; 309 [86.1%] White); those randomized to SC had a mean age of 34.1 (10.0) years (102 [45.3%] men; 75 [34.7%] Hispanic or Latino; 6 [2.7%] Black; 190 [84.4%] White). All casirivimab and imdevimab treatments showed significant virologic reduction through day 7. Least-squares mean differences in TWACB viral load for casirivimab and imdevimab vs placebo ranged from –0.56 (95% CI; –0.89 to –0.24) log(10) copies/mL for the 1200-mg IV dose to –0.71 (95% CI, –1.05 to –0.38) log(10) copies/mL for the 2400-mg IV dose. There were no adverse safety signals or dose-related safety findings, grade 2 or greater infusion-related or hypersensitivity reactions, grade 3 or greater injection-site reactions, or fatalities. Two serious adverse events not related to COVID-19 or the study drug were reported. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial including outpatients with asymptomatic and low-risk symptomatic SARS-CoV-2, all IV and SC doses of casirivimab and imdevimab comparably reduced viral load. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04666441 American Medical Association 2022-08-15 /pmc/articles/PMC9379747/ /pubmed/35969402 http://dx.doi.org/10.1001/jamanetworkopen.2022.25411 Text en Copyright 2022 Portal-Celhay C et al. JAMA Network Open. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License.
spellingShingle Original Investigation
Portal-Celhay, Cynthia
Forleo-Neto, Eduardo
Eagan, Will
Musser, Bret J.
Davis, John D.
Turner, Kenneth C.
Norton, Thomas
Hooper, Andrea T.
Hamilton, Jennifer D.
Pan, Cynthia
Mahmood, Adnan
Baum, Alina
Kyratsous, Christos A.
Kim, Yunji
Parrino, Janie
Kampman, Wendy
Roque-Guerrero, Lilia
Stoici, Roxana
Fatakia, Adil
Soo, Yuhwen
Geba, Gregory P.
Kowal, Bari
DiCioccio, A. Thomas
Stahl, Neil
Lipsich, Leah
Braunstein, Ned
Herman, Gary A.
Yancopoulos, George D.
Weinreich, David M.
Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial
title Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial
title_full Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial
title_fullStr Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial
title_full_unstemmed Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial
title_short Virologic Efficacy of Casirivimab and Imdevimab COVID-19 Antibody Combination in Outpatients With SARS-CoV-2 Infection: A Phase 2 Dose-Ranging Randomized Clinical Trial
title_sort virologic efficacy of casirivimab and imdevimab covid-19 antibody combination in outpatients with sars-cov-2 infection: a phase 2 dose-ranging randomized clinical trial
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379747/
https://www.ncbi.nlm.nih.gov/pubmed/35969402
http://dx.doi.org/10.1001/jamanetworkopen.2022.25411
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