Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S.
Ad26COVS1
/ adverse effects
Adolescent
Adult
COVID-19
/ epidemiology
Double-Blind Method
Follow-Up Studies
Hospitalization
/ statistics & numerical data
Humans
Immunogenicity, Vaccine
Kaplan-Meier Estimate
Middle Aged
Patient Acuity
SARS-CoV-2
Vaccine Efficacy
/ statistics & numerical data
Young Adult
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:
03 03 2022
03 03 2022
Historique:
pubmed:
10
2
2022
medline:
16
3
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
The Ad26.COV2.S vaccine was highly effective against severe-critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis. We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×10 Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe-critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe-critical Covid-19 (with only 4 severe-critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19-related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified. A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe-critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.).
Sections du résumé
BACKGROUND
The Ad26.COV2.S vaccine was highly effective against severe-critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis.
METHODS
We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×10
RESULTS
Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe-critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe-critical Covid-19 (with only 4 severe-critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19-related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified.
CONCLUSIONS
A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe-critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.).
Identifiants
pubmed: 35139271
doi: 10.1056/NEJMoa2117608
pmc: PMC8849184
doi:
Substances chimiques
Ad26COVS1
JT2NS6183B
Banques de données
ClinicalTrials.gov
['NCT04505722']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
847-860Subventions
Organisme : NIH HHS
ID : UM1 AI148684
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069476
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069534
Pays : United States
Organisme : NIAAA NIH HHS
ID : HHSO100201700018C
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068614
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068618
Pays : United States
Organisme : NIH HHS
ID : UM1 AI68619
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI161175
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069476
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148576
Pays : United States
Organisme : NIH HHS
ID : UM1 AI68635
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069470
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148685
Pays : United States
Organisme : NIH HHS
ID : UM1 AI148373
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148452
Pays : United States
Organisme : NIH HHS
ID : UM1 AI148685
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069470
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148373
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI068636
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148684
Pays : United States
Organisme : NIH HHS
ID : UM1 AI68618
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069452
Pays : United States
Organisme : NIH HHS
ID : UM1 AI148452
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069463
Pays : United States
Organisme : NIH HHS
ID : UM1 AI68614
Pays : United States
Organisme : NIH HHS
ID : UM1 AI68636
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
Organisme : NIH HHS
ID : UM1 AI148576
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068619
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068636
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068617
Pays : United States
Investigateurs
Janet S Lee
(JS)
Brian T Garibaldi
(BT)
Charles Shey Wiysonge
(CS)
Anoma Nellore
(A)
Timothy E Albertson
(TE)
Christian Sandrock
(C)
Victor F Tapson
(VF)
Richard Gorman
(R)
Carmen A Paez
(CA)
James Kublin
(J)
Simbarashe G Takuva
(SG)
Alex Greninger
(A)
Pavitra Roychoudhury
(P)
Robert W Coombs
(RW)
Keith R Jerome
(KR)
Kimberly L Taylor
(KL)
Flora Castellino
(F)
Xiaomi Tong
(X)
Corrina Pavetto
(C)
Teletha Gipson
(T)
Tina Tong
(T)
Marina Lee
(M)
James Zhou
(J)
Michael Fay
(M)
Daniel Wolfe
(D)
Peter B Gilbert
(PB)
Ollivier Hyrien
(O)
Alex Luedtke
(A)
Hein Fennema
(H)
Kim Offergeld
(K)
Nancy Cauwenberghs
(N)
Tamzin Tanner
(T)
Kelly McQuarrie
(K)
Chimeremma Nnadi
(C)
Obiageli Sogbetun
(O)
Nina Ahmad
(N)
Ian De Proost
(I)
Cyrus Hoseyni
(C)
Paul Coplan
(P)
Najat Khan
(N)
Peter Ronco
(P)
Sanne Roels
(S)
Daniel Backenroth
(D)
Jennifer Bogert
(J)
Fei Chen
(F)
Pei-Ling Chu
(PL)
Kimberly Cooper
(K)
Hilde Delanghe
(H)
John T Jones
(JT)
Monika Peeters
(M)
Willem Talloen
(W)
Jose Pinheiro
(J)
Ilse Scheys
(I)
Pallavi Shetti
(P)
Nathalie Vaissiere
(N)
Jose Salas
(J)
Molli Imola Sandor
(MI)
Jiajun Xu
(J)
Dawn Furey
(D)
Jodi Meck
(J)
Boerries Brandenburg
(B)
Jenny Hendriks
(J)
Jarek Juraszek
(J)
Anne Marit de Groot
(AM)
Griet Van Roey
(G)
Dirk Heerwegh
(D)
Judith Aberg
(J)
Mark Adams
(M)
Michael Adams
(M)
Samuel Aguayo
(S)
Habibul Ahsan
(H)
Diego Aizenberg
(D)
Augusto Alonto
(A)
Maria Fernanda Alzogaray
(MF)
Evan Anderson
(E)
Jorge Andrade Pinto
(JA)
Forest W Arnold
(FW)
Clóvis Arns da Cunha
(CAD)
Vivian Avelino Silva
(VA)
Sharlaa Badal-Faesen
(S)
Lindsey Baden
(L)
Shaun Barnabas
(S)
Roger Bedimo
(R)
Linda-Gail Bekker
(LG)
Mezgebe Berhe
(M)
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(M)
Martin J Blaser
(MJ)
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(PE)
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(T)
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(CR)
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Daniel Brune
(D)
Robert Buynak
(R)
Carlos Antonio Cabrera May
(CA)
Andres Angelo Cadena Bonfanti
(AA)
Pedro Cahn
(P)
Jeffrey L Carson
(JL)
Wilfredo Martin Casapia Morales
(WM)
Lidia Isabel Cassetti
(LI)
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(LS)
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(JD)
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(M)
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(L)
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(K)
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(A)
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(RE)
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(R)
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(JV)
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(M)
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(IC)
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(B)
Jaime Restrepo
(J)
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(H)
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(M)
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(E)
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(DJ)
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(LA)
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(M)
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