Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
09 06 2022
09 06 2022
Historique:
pubmed:
21
4
2022
medline:
11
6
2022
entrez:
20
4
2022
Statut:
ppublish
Résumé
The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days. In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183. A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group. A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).
Sections du résumé
BACKGROUND
The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.
METHODS
In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183.
RESULTS
A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group.
CONCLUSIONS
A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).
Identifiants
pubmed: 35443106
doi: 10.1056/NEJMoa2116620
pmc: PMC9069994
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antiviral Agents
0
Drug Combinations
0
cilgavimab and tixagevimab drug combination
0
tixagevimab
0
cilgavimab
1KUR4BN70F
Banques de données
ClinicalTrials.gov
['NCT04625725']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
2188-2200Subventions
Organisme : U.S. Department of Health and Human Services
ID : W911QY-21-9-0001
Organisme : U.S. Department of Defense
ID : W911QY-21-9-0001
Investigateurs
David Pham
(D)
Luis T Casanova
(LT)
Hilde Bollen
(H)
Ine Vercammen
(I)
Mirjam de Maeyer
(M)
Erik Buntinx
(E)
Linde Buntinx
(L)
Samir Arora
(S)
Lindsay Newton
(L)
Priyantha Wijewardane
(P)
Luc Capiau
(L)
Christiane Snoeck
(C)
Faisal Amin
(F)
Haroon Hafeez
(H)
Thomas Guimard
(T)
Akash G Manjunathappa
(AG)
Henri Laurichesse
(H)
Christine Vallejo
(C)
Rachel Froget
(R)
Caroline Caille-Fenerol
(C)
Clémentine Ruch
(C)
Maxime Luu
(M)
Marc Bardou
(M)
Audrey Guillier
(A)
Hervé Devilliers
(H)
Rogier Thomas
(R)
Francois Raffi
(F)
Clotilde Allavena
(C)
Anne-Sophie Lecompte
(AS)
Elisabeth Botelho-Nevers
(E)
José Fernandes
(J)
Frédérique Bertholon
(F)
Sara Llerena
(S)
Eileen Jimenez
(E)
Bertha M Cano
(BM)
Veronica Bello
(V)
Lidice Chateloin
(L)
Maria V Cano
(MV)
Patricia González Cediel
(P)
Gricel Cano
(G)
Marilda Cano Zaldivar
(M)
Felisa Aleman
(F)
Jonathan Yousef
(J)
Melissa Vila
(M)
Ryan J DeWeese
(RJ)
Mark Vishnepolsky
(M)
Adam Frome
(A)
Sharad Sathyan
(S)
Sina Raissi
(S)
Helen Brickel
(H)
Robert Lynn
(R)
Melissa Marine
(M)
Gabriela Mendoza
(G)
Ronald Ralph
(R)
Cynthia Moka
(C)
Heather DiMarco
(H)
Michelle Cordero
(M)
Jeffrey Connaire
(J)
Vinayak Ramanath
(V)
Ferdinand Alcaide
(F)
Rajendran Alappan
(R)
Tamorie Smith
(T)
German Hernandez
(G)
Steven Zeig
(S)
Neal Patel
(N)
Dominique Deplanque
(D)
Elise Elrezzi
(E)
Romain Barus
(R)
Juliette De Langhe
(J)
Maria-Claire Migaud
(MC)
Stéphanie Somers
(S)
Jean-Michel Molina
(JM)
Dyhia Sardou-Rabia
(D)
Leal Alexander
(L)
Florencia Etcheverry
(F)
Marta Aldea
(M)
Jocelyn Nava
(J)
Omar Anagua
(O)
Jesse Anagua Melendres
(J)
José Maria Ignacio García
(JM)
Vicente Estrada Perez
(V)
Eva Santiago
(E)
Jose María Echave-Sustaeta
(JM)
Lorena Comeche Casanova
(L)
Alfonso Cruz Jentoft
(A)
Jesús Mateos Del Nozal
(JM)
María Dolores Ochoa Castillo
(MD)
Juan F Zapata
(JF)
Clarence McMillan
(C)
Dennis L Ross
(DL)
Angie Anderson
(A)
Brian Siu
(B)
David Wilson
(D)
Yelena Quintanilla
(Y)
Marc de Meulemeester
(M)
Ogechika Alozie
(O)
Jose Burgos
(J)
Brandon J Essink
(BJ)
Laura Falcone
(L)
Roni Gray
(R)
Robert Onder
(R)
Michael Dao
(M)
Diego Torres
(D)
Mira Baron
(M)
Eric Bolster
(E)
John Ndikum
(J)
David Biles
(D)
David Ball
(D)
Mahadev Ramjee
(M)
Liana Dunn
(L)
Ellie Howie
(E)
Siobhan Reilly
(S)
Greg Sullivan
(G)
Rajiv Parikh
(R)
Nathanael Wright
(N)
Jean-Benoit Martinot
(JB)
Ibrahim Menendez-Perez
(I)
Lawrence Barnes
(L)
Susie Keast
(S)
Nicola Donlin
(N)
Amelia Lewis
(A)
Jayant Kumar
(J)
Edison Tan
(E)
Judith Betts
(J)
Jodumutt Bhat
(J)
Alison Uriel
(A)
Asghar Chaudhry
(A)
Radu Jacob
(R)
Edouard Martin
(E)
Ojeifo Akharia
(O)
Sherif George Naguib
(SG)
Ghazaleh Bahrami
(G)
Nelson So
(N)
Margarita Nunez
(M)
Richard L Montgomery
(RL)
William F Hopper
(WF)
Shavonna Haamid
(S)
Stephanie Riggs
(S)
Dominique Smith
(D)
Lisa Crihfield
(L)
Julia Kordsmeier
(J)
Nicola Longley
(N)
Tommy Rampling
(T)
Vincenzo Libri
(V)
Shama Hamal
(S)
Sarah Whittley
(S)
Marivic Ricamara
(M)
Claudia Ismail
(C)
Yee Ting Nicole Yim
(YTN)
Yee-Chin Lee
(YC)
Holly Baker
(H)
Todd Rawlins
(T)
Kirsty Adams
(K)
Catherine Houlihan
(C)
Edgard Vera
(E)
Michelle Owens
(M)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2022 Massachusetts Medical Society.
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