Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult.

Summary

This study will assess the safety and efficacy of a single dose of AZD7442(× 2 IM injections) compared to placebo for the prevention of COVID-19.

Timeline

Start

2020-11-21

Primary completion

2022-08-16

Completion

2023-12-08

Outcome

Met primary endpoint

registry analysis (superiority test); AZD7442 vs Placebo; p <0.001; Relative Risk Reduction 76.73 (95% CI 46.05 to 89.96); Poisson regression NCT04625725 ↗

paper 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) PMID 35443106 ↗

release “PROVENT Phase III pre-exposure prophylaxis trial showed AstraZeneca's AZD7442 achieved a statistically significant reduction in the incidence of symptomatic COVID-19, the trial's primary endpoint.” astrazeneca.com ↗

release “PROVENT Phase III pre-exposure prophylaxis (prevention) trial showed that AstraZeneca’s Evusheld (tixagevimab and cilgavimab), formerly AZD7442, reduced the risk of developing symptomatic COVID-19 by 77%” astrazeneca.com ↗

Publications

• Background Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Ozguroglu M; PACIFIC Investigators. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25.
• 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 Domachowske JB, Khan AA, Esser MT, Jensen K, Takas T, Villafana T, Dubovsky F, Griffin MP. Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants. Pediatr Infect Dis J. 2018 Sep;37(9):886-892. doi: 10.1097/INF.0000000000001916.
• Background Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M, Breedveld FC, D'Amelio R, Dougados M, Kapetanovic MC, van Laar JM, de Thurah A, Landewe RB, Molto A, Muller-Ladner U, Schreiber K, Smolar L, Walker J, Warnatz K, Wulffraat NM, Elkayam O. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020 Jan;79(1):39-52. doi: 10.1136/annrheumdis-2019-215882. Epub 2019 Aug 14.
• Background Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020 Apr;5(4):536-544. doi: 10.1038/s41564-020-0695-z. Epub 2020 Mar 2.
• Background Griffin MP, Khan AA, Esser MT, Jensen K, Takas T, Kankam MK, Villafana T, Dubovsky F. Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended Half-Life, in Healthy Adults. Antimicrob Agents Chemother. 2017 Feb 23;61(3):e01714-16. doi: 10.1128/AAC.01714-16. Print 2017 Mar.
• Background Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, Simoes EAF, Esser MT, Khan AA, Dubovsky F, Villafana T, DeVincenzo JP; Nirsevimab Study Group. Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. N Engl J Med. 2020 Jul 30;383(5):415-425. doi: 10.1056/NEJMoa1913556.
• Background Lamb EJ, Levey AS, Stevens PE. The Kidney Disease Improving Global Outcomes (KDIGO) guideline update for chronic kidney disease: evolution not revolution. Clin Chem. 2013 Mar;59(3):462-5. doi: 10.1373/clinchem.2012.184259. No abstract available.
• 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 Morand EF, Furie RA. Anifrolumab in Systemic Lupus Erythematosus. Reply. N Engl J Med. 2020 Apr 23;382(17):1666. doi: 10.1056/NEJMc2002191. No abstract available.
• Background Poland GA, Ovsyannikova IG, Kennedy RB. Personalized vaccinology: A review. Vaccine. 2018 Aug 28;36(36):5350-5357. doi: 10.1016/j.vaccine.2017.07.062. Epub 2017 Jul 31.
• Background Robbie GJ, Criste R, Dall'acqua WF, Jensen K, Patel NK, Losonsky GA, Griffin MP. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013 Dec;57(12):6147-53. doi: 10.1128/AAC.01285-13. Epub 2013 Sep 30.
• Background Wagner A, Weinberger B. Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives. Front Immunol. 2020 Apr 23;11:717. doi: 10.3389/fimmu.2020.00717. eCollection 2020.
• Background WHO. WHO Coronavirus Disease (COVID-19) Dashboard. 2020a.
• Background WHO. WHO R&D Blueprint COVID-19 Therapeutic Trial Synopsis Draft 18 February 2020. https://www.who.int/blueprint/priority-diseases/key-action/COVID19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf. Published 2020b. Accessed 25 September 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 Zimmermann P, Curtis N. Factors That Influence the Immune Response to Vaccination. Clin Microbiol Rev. 2019 Mar 13;32(2):e00084-18. doi: 10.1128/CMR.00084-18. Print 2019 Mar 20.
• 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.
• Ustianowski A, Levin MJ, De Wit S, Launay O, Veekmans B, Rampling T, Sullivan JG, Vishnepolsky M, Wijewardane P, Fawadleh Y, Zhang H, Li M, Wickramarachchi D, Sharbaugh A, Beavon R, Thissen J, Hirao L, Dzutseva V, Seegobin S, Streicher K, Kiazand A, Esser MT, Chang LJ, Perez JL, Cohen TS. Safety and Pharmacokinetics of Repeat Dosing of Long-Acting SARS-CoV-2 Antibodies Tixagevimab/Cilgavimab (AZD7442): Results from the PROVENT Sub-study. Clin Drug Investig. 2026 Feb;46(2):207-219. doi: 10.1007/s40261-025-01515-x. Epub 2026 Jan 16.
• Levin MJ, Ustianowski A, De Wit S, Beavon R, Thissen J, Seegobin S, Dey K, Near KA, Streicher K, Kiazand A, Esser MT. Efficacy, Safety, and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Prevention of Symptomatic COVID-19: 15-Month Final Analysis of the PROVENT and STORM CHASER Trials. Infect Dis Ther. 2024 Jun;13(6):1253-1268. doi: 10.1007/s40121-024-00970-x. Epub 2024 May 4.
• Tuffy KM, Ahani B, Aksyuk AA, Avila M, Brady T, Kijak GH, Koh G, Levin MJ, Roe TL, Schuko N, Thissen J, Ustianowski A, Zhang T, Kelly EJ, Streicher K. Breakthrough SARS-CoV-2 Infections in the PROVENT Prevention Trial Were Not Associated With AZD7442 (Tixagevimab/Cilgavimab) Resistant Variants. J Infect Dis. 2023 Oct 18;228(8):1055-1059. doi: 10.1093/infdis/jiad210.
• Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
• Levin MJ, Ustianowski A, De Wit S, Launay O, Avila M, Templeton A, Yuan Y, Seegobin S, Ellery A, Levinson DJ, Ambery P, Arends RH, Beavon R, Dey K, Garbes P, Kelly EJ, Koh GCKW, Near KA, Padilla KW, Psachoulia K, Sharbaugh A, Streicher K, Pangalos MN, Esser MT; PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022 Jun 9;386(23):2188-2200. doi: 10.1056/NEJMoa2116620. Epub 2022 Apr 20.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	AZD7442	Monoclonal antibody	300 mg	Intramuscular
Subject	AZD7442	Monoclonal antibody	600 mg	Intramuscular

Indications