Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults

Summary

The aim of the study is to assess the safety, efficacy, and immunogenicity of AZD1222 for the prevention of COVID-19.

Timeline

Start

2020-08-28

Primary completion

2021-03-05

Completion

2023-02-10

Outcome

Met primary endpoint

registry analysis (superiority test); AZD1222 vs Placebo; p <0.001; Vaccine efficacy 73.98 (95% CI 65.34 to 80.47); NCT04516746 ↗

release “The AstraZeneca US Phase III trial of AZD1222 demonstrated statistically significant vaccine efficacy of 79%” astrazeneca.com ↗

Publications

• Background CDC. (Centers for Disease Control and Prevention). Coronavirus Disease 2019 (COVID-19), Symptoms of Coronavrus. https://www.cdc.gov/coronavirus/2019-ncov/symptomstesting/ symptoms.html. Published 2020. Accessed 01 July 2020.
• Background FDA. (Food and Drug Administration). Guidance for Industry. Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. . https://www.fda.gov/media/73679/download. Published 2007. Accessed 20 June 2020.
• Background Folegatti PM, Bittaye M, Flaxman A, Lopez FR, Bellamy D, Kupke A, Mair C, Makinson R, Sheridan J, Rohde C, Halwe S, Jeong Y, Park YS, Kim JO, Song M, Boyd A, Tran N, Silman D, Poulton I, Datoo M, Marshall J, Themistocleous Y, Lawrie A, Roberts R, Berrie E, Becker S, Lambe T, Hill A, Ewer K, Gilbert S. Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial. Lancet Infect Dis. 2020 Jul;20(7):816-826. doi: 10.1016/S1473-3099(20)30160-2. Epub 2020 Apr 21.
• Background Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu Rev Virol. 2016 Sep 29;3(1):237-261. doi: 10.1146/annurev-virology-110615-042301. Epub 2016 Aug 25.
• Background Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574. doi: 10.1016/S0140-6736(20)30251-8. Epub 2020 Jan 30.
• Background SPEAC. (Safety Platform for Emergency Vaccines) D2.3 Priority list of adverse events of special interest: COVID-19. Work Package: WP2 Standards and Tools. v1.1. 05 March 2020. https://media.tghn.org/articles/COVID-19_AESIs_SPEAC_V1.1_5Mar2020.pdf. Published 2020. Accessed 14 June 2020.
• Background van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR, Avanzato VA, Bushmaker T, Flaxman A, Ulaszewska M, Feldmann F, Allen ER, Sharpe H, Schulz J, Holbrook M, Okumura A, Meade-White K, Perez-Perez L, Edwards NJ, Wright D, Bissett C, Gilbride C, Williamson BN, Rosenke R, Long D, Ishwarbhai A, Kailath R, Rose L, Morris S, Powers C, Lovaglio J, Hanley PW, Scott D, Saturday G, de Wit E, Gilbert SC, Munster VJ. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020 Oct;586(7830):578-582. doi: 10.1038/s41586-020-2608-y. Epub 2020 Jul 30.
• Background Waldrop G, Doherty M, Vitoria M, Ford N. Stable patients and patients with advanced disease: consensus definitions to support sustained scale up of antiretroviral therapy. Trop Med Int Health. 2016 Sep;21(9):1124-30. doi: 10.1111/tmi.12746. Epub 2016 Jul 22.
• Background WHO. (World Health Organization) Coronavirus disease (COVID-19) situation report-175. 13 July 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200713- covid-19-sitrep-175.pdf?sfvrsn=d6acef25_2. Published 2020. Accessed 13 July 2020.
• Background Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.
• Background Clinical Study Protocol - 1.0 AstraZeneca AZD1222 - D8110C00001 CONFIDENTIAL AND PROPRIETARY 92 of 92
• Background Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004 Apr 1;159(7):702-6. doi: 10.1093/aje/kwh090.
• Janes H, Fisher LH, Kee JJ, Parameswaran L, Goepfert PA, Falsey AR, Ludwig J, Magaret CA, Gilbert PB, Kublin JG, Rouphael N, Sobieszczyk ME, El Sahly HM, Baden LR, Grinsztejn B, Walsh SR, Gray GE, Kotloff KL, Gay CL, Greninger AL, Tapia MD, Hammershaimb EA, Priddy FH, Green JA, Struyf F, Dunkle L, Neuzil KM, Corey L, Huang Y. Association Between SARS-CoV-2 Viral Load and COVID-19 Vaccination in 4 Phase 3 Trials. J Infect Dis. 2024 Dec 16;230(6):1384-1389. doi: 10.1093/infdis/jiae400.
• Moore M, Zhu Y, Hirsch I, White T, Reiner RC, Barber RM, Pigott D, Collins JK, Santoni S, Sobieszczyk ME, Janes H. Estimating vaccine efficacy during open-label follow-up of COVID-19 vaccine trials based on population-level surveillance data. Epidemics. 2024 Jun;47:100768. doi: 10.1016/j.epidem.2024.100768. Epub 2024 Apr 15.
• Turley CB, Tables L, Fuller T, Sanders LJ, Scott H, Moodley A, Woodward Davis A, Leav B, Miller J, Schoemaker K, Vandebosch A, Sadoff J, Woo W, Cho I, Dunkle LM, Li S, van der Laan L, Gilbert PB, Follmann D, Jaynes H, Kublin JG, Baden LR, Goepfert P, Kotloff K, Gay CL, Falsey AR, El Sahly HM, Sobieszczyk ME, Huang Y, Neuzil KM, Corey L, Grinsztejn B, Gray G, Rouphael N, Luedtke A; COVID-19 Prevention Network CoVPN. Modifiers of COVID-19 vaccine efficacy: Results from four COVID-19 prevention network efficacy trials. Vaccine. 2023 Jul 25;41(33):4899-4906. doi: 10.1016/j.vaccine.2023.06.066. Epub 2023 Jun 23.
• Maaske J, Sproule S, Falsey AR, Sobieszczyk ME, Luetkemeyer AF, Paulsen GC, Riddler SA, Robb ML, Rolle CP, Sha BE, Tong T, Ahani B, Aksyuk AA, Bansal H, Egan T, Jepson B, Padilla M, Patel N, Shoemaker K, Stanley AM, Swanson PA, Wilkins D, Villafana T, Green JA, Kelly EJ. Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated. Front Immunol. 2023 Jan 13;13:1062067. doi: 10.3389/fimmu.2022.1062067. eCollection 2022.
• Aksyuk AA, Bansal H, Wilkins D, Stanley AM, Sproule S, Maaske J, Sanikommui S, Hartman WR, Sobieszczyk ME, Falsey AR, Kelly EJ. AZD1222-induced nasal antibody responses are shaped by prior SARS-CoV-2 infection and correlate with virologic outcomes in breakthrough infection. Cell Rep Med. 2023 Jan 17;4(1):100882. doi: 10.1016/j.xcrm.2022.100882. Epub 2022 Dec 15.
• Sobieszczyk ME, Maaske J, Falsey AR, Sproule S, Robb ML, Frenck RW Jr, Tieu HV, Mayer KH, Corey L, Neuzil KM, Tong T, Brewinski Isaacs M, Janes H, Bansal H, Edwards LM, Green JA, Kelly EJ, Shoemaker K, Takas T, White T, Bhuyan P, Villafana T, Hirsch AI; AstraZeneca AZD1222 Clinical Study Group. Durability of protection and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine over 6 months. J Clin Invest. 2022 Sep 15;132(18):e160565. doi: 10.1172/JCI160565.
• Falsey AR, Sobieszczyk ME, Hirsch I, Sproule S, Robb ML, Corey L, Neuzil KM, Hahn W, Hunt J, Mulligan MJ, McEvoy C, DeJesus E, Hassman M, Little SJ, Pahud BA, Durbin A, Pickrell P, Daar ES, Bush L, Solis J, Carr QO, Oyedele T, Buchbinder S, Cowden J, Vargas SL, Guerreros Benavides A, Call R, Keefer MC, Kirkpatrick BD, Pullman J, Tong T, Brewinski Isaacs M, Benkeser D, Janes HE, Nason MC, Green JA, Kelly EJ, Maaske J, Mueller N, Shoemaker K, Takas T, Marshall RP, Pangalos MN, Villafana T, Gonzalez-Lopez A; AstraZeneca AZD1222 Clinical Study Group. Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine. N Engl J Med. 2021 Dec 16;385(25):2348-2360. doi: 10.1056/NEJMoa2105290. Epub 2021 Sep 29.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	AZD1222	Vaccine	—	Intramuscular

Indications