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 - PubMed (original) (raw)

Randomized Controlled Trial

. 2021 Jan 9;397(10269):99-111.

doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8.

Sue Ann Costa Clemens 2, Shabir A Madhi 3, Lily Y Weckx 4, Pedro M Folegatti 5, Parvinder K Aley 1, Brian Angus 5, Vicky L Baillie 6, Shaun L Barnabas 7, Qasim E Bhorat 8, Sagida Bibi 1, Carmen Briner 9, Paola Cicconi 5, Andrea M Collins 10, Rachel Colin-Jones 1, Clare L Cutland 6, Thomas C Darton 11, Keertan Dheda 12, Christopher J A Duncan 13, Katherine R W Emary 1, Katie J Ewer 5, Lee Fairlie 14, Saul N Faust 15, Shuo Feng 1, Daniela M Ferreira 10, Adam Finn 16, Anna L Goodman 17, Catherine M Green 18, Christopher A Green 19, Paul T Heath 20, Catherine Hill 14, Helen Hill 10, Ian Hirsch 21, Susanne H C Hodgson 5, Alane Izu 22, Susan Jackson 5, Daniel Jenkin 5, Carina C D Joe 5, Simon Kerridge 1, Anthonet Koen 22, Gaurav Kwatra 14, Rajeka Lazarus 23, Alison M Lawrie 5, Alice Lelliott 1, Vincenzo Libri 24, Patrick J Lillie 25, Raburn Mallory 21, Ana V A Mendes 26, Eveline P Milan 27, Angela M Minassian 5, Alastair McGregor 28, Hazel Morrison 5, Yama F Mujadidi 1, Anusha Nana 9, Peter J O'Reilly 1, Sherman D Padayachee 29, Ana Pittella 30, Emma Plested 1, Katrina M Pollock 31, Maheshi N Ramasamy 1, Sarah Rhead 1, Alexandre V Schwarzbold 32, Nisha Singh 1, Andrew Smith 33, Rinn Song 34, Matthew D Snape 1, Eduardo Sprinz 35, Rebecca K Sutherland 36, Richard Tarrant 18, Emma C Thomson 37, M Estée Török 38, Mark Toshner 39, David P J Turner 40, Johan Vekemans 21, Tonya L Villafana 21, Marion E E Watson 5, Christopher J Williams 41, Alexander D Douglas 5, Adrian V S Hill 5, Teresa Lambe 5, Sarah C Gilbert 5, Andrew J Pollard 42; Oxford COVID Vaccine Trial Group

Collaborators, Affiliations

Randomized Controlled Trial

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

Merryn Voysey et al. Lancet. 2021.

Erratum in

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.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

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Figures

Figure

Figure

Kaplan-Meier cumulative incidence of primary symptomatic, NAAT-positive COVID-19 Cumulative incidence of symptomatic COVID-19 after two doses (left) or after first standard dose in participants receiving only standard-dose vaccines (right). Grey shaded areas show the exclusion period after each dose in which cases were excluded from the analysis. Blue and red shaded areas show 95% CIs. LD/SD=low-dose prime plus standard-dose boost. MenACWY=meningococcal group A, C, W, and Y conjugate vaccine. NAAT=nucleic acid amplification test. SD/SD=two standard-dose vaccines given.

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