Merryn Voysey
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Voysey, Merryn; Costa Clemens, Sue Ann; Madhi, Shabir A.; Weckx, Lily Y.; Folegatti, Pedro M.; Aley, Parvinder K.; Angus, Brian; Baillie, Vicky L.; Barnabas, Shaun L.; Bhorat, Qasim E.; Bibi, Sagida; Briner, Carmen; Cicconi, Paola; Collins, Andrea M.; Colin-Jones, Rachel; Cutland, Clare L.; Darton, Thomas C.; Dheda, Keertan; Duncan, Christopher J. A.; Emary, Katherine R. W.; Ewer, Katie J.; Fairlie, Lee; Faust, Saul N.; Feng, Shuo; Ferreira, Daniela M.; Finn, Adam; Goodman, Anna L.; Green, Catherine M.; Green, Christopher A.; Heath, Paul T.; Hill, Catherine; Hill, Helen; Hirsch, Ian; Hodgson, Susanne H. C.; Izu, Alane; Jackson, Susan; Jenkin, Daniel; Joe, Carina C. D.; Kerridge, Simon; Koen, Anthonet; Kwatra, Gaurav; Lazarus, Rajeka; Lawrie, Alison M.; Lelliott, Alice; Libri, Vincenzo; Lillie, Patrick J.; Mallory, Raburn; Mendes, Ana V. A.; Milan, Eveline P.; Minassian, Angela M.; McGregor, Alastair; Morrison, Hazel; Mujadidi, Yama F.; Nana, Anusha; O?Reilly, Peter J.; Padayachee, Sher...
Authors
Sue Ann Costa Clemens
Shabir A. Madhi
Lily Y. Weckx
Pedro M. Folegatti
Parvinder K. Aley
Brian Angus
Vicky L. Baillie
Shaun L. Barnabas
Qasim E. Bhorat
Sagida Bibi
Carmen Briner
Paola Cicconi
Andrea M. Collins
Rachel Colin-Jones
Clare L. Cutland
Thomas C. Darton
Keertan Dheda
Christopher J. A. Duncan
Katherine R. W. Emary
Katie J. Ewer
Lee Fairlie
Saul N. Faust
Shuo Feng
Daniela M. Ferreira
Adam Finn
Anna L. Goodman
Catherine M. Green
Christopher A. Green
Paul T. Heath
Catherine Hill
Helen Hill
Ian Hirsch
Susanne H. C. Hodgson
Alane Izu
Susan Jackson
Daniel Jenkin
Carina C. D. Joe
Simon Kerridge
Anthonet Koen
Gaurav Kwatra
Rajeka Lazarus
Alison M. Lawrie
Alice Lelliott
Vincenzo Libri
Patrick J. Lillie
Raburn Mallory
Ana V. A. Mendes
Eveline P. Milan
Angela M. Minassian
Alastair McGregor
Hazel Morrison
Yama F. Mujadidi
Anusha Nana
Peter J. O�Reilly
Sherman D. Padayachee
Ana Pittella
Emma Plested
Katrina M. Pollock
Maheshi N. Ramasamy
Sarah Rhead
Alexandre V. Schwarzbold
Nisha Singh
Andrew Smith
Rinn Song
Matthew D. Snape
Eduardo Sprinz
Rebecca K. Sutherland
Richard Tarrant
Emma C. Thomson
M. Est�e T�r�k
Mark Toshner
David P. J. Turner
Johan Vekemans
Tonya L. Villafana
Marion E. E. Watson
Christopher J. Williams
Alexander D. Douglas
Adrian V. S. Hill
Teresa Lambe
Sarah C. Gilbert
Andrew J. Pollard
Oxford COVID Vaccine Trial Group
Abstract
Background
A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.
Methods
This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.
Findings
Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.
Interpretation
ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
Funding
UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
Journal Article Type | Article |
---|---|
Online Publication Date | Dec 8, 2020 |
Publication Date | Jan 7, 2021 |
Deposit Date | Feb 9, 2021 |
Publicly Available Date | Feb 9, 2021 |
Print ISSN | 0140-6736 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 397 |
Issue | 10269 |
Pages | 99-111 |
DOI | https://doi.org/10.1016/S0140-6736%2820%2932661-1 |
Keywords | Covid-19 |
Public URL | http://researchrepository.napier.ac.uk/Output/2736384 |
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Safety And Efficacy Of The ChAdOx1 NCoV-19 Vaccine (AZD1222) Against SARS-CoV-2: An Interim Analysis Of Four Randomised Controlled Trials In Brazil, South Africa, And The UK
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Copyright Statement
© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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