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

NCT04516746 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: D8110C000012020-005226-28
• Study Type: interventional
• Target: 32,450
• Locations: 3 countries
• Sites: 84

Brief Summary

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

Conditions

COVID-19; SARS-CoV-2

Keywords

COVID-19 Vaccine

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Binary Response

  A binary response, whereby a participant with negative serostatus at baseline is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case. The primary efficacy analysis was performed once approximately 150 events meeting the primary efficacy outcome measure definition had occurred across the AZD1222 and placebo groups.

  From 15 days post second dose up to data cut-off date (DCO) of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks

• Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention

  An AE is the development of any untoward medical occurrence in a clinical study participant administered medicinal product and which does not necessarily have a causal relationship with this medicinal product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  From Day 1 up to 28 days post second dose of study intervention, approximately 57 days

• Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination

  An SAE is an AE occurring during any study phase that fulfils 1 or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. AESIs were events of scientific and medical interest specific to the further understanding of the study intervention safety profile and required close monitoring and rapid communication by the investigators to the sponsor. MAAEs are defined as AEs leading to medically-attended visits that were not routine visits for physical examination or vaccination, such as an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Different follow-up time between AZD1222 and Placebo groups (20223 versus 3893 participant years).

  From Day 1 up to receipt of non-study COVID-19 vaccination or a maximum of Day 760 for participants without non-study COVID-19 vaccination.

• Number of Participants With Local and Systemic Solicited AEs in the Substudy Only

  Solicited AEs are local or systemic predefined events for assessment of reactogenicity. Solicited AEs were collected in a e-Diary only for participants in the substudy.

  From Day 1 up to 7 days post each dose of study intervention, approximately 14 days

Secondary Outcomes (14)

• Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Post Second Dose of Study Intervention

  From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks

• Number of Participants With First COVID-19 Symptomatic Illness Using Centers for Disease Control and Prevention (CDC) Criteria Post Second Dose of Study Intervention

  From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks

• Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Post Second Dose of Study Intervention

  From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks

• Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Post Second Dose of Study Intervention

  From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks

• Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post Second Dose of Study Intervention

  From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks

Study Arms (2)

AZD1222

EXPERIMENTAL

Approximately 20,000 participants randomized to the AZD1222 arm

Biological: AZD1222

Placebo

PLACEBO COMPARATOR

Approximately 10,000 participants randomized to the saline placebo arm

Biological: Placebo

Interventions

AZD1222 BIOLOGICAL

AZD1222 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2-5 surface glycoprotein.

AZD1222

Placebo BIOLOGICAL

Commercially available 0.9% (n/V) saline for injection.

Placebo

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Increased risk of SARS-CoV-2 infection
• Medically stable

You may not qualify if:

• confirmed or suspected immunosuppressive or immunodeficient state
• significant disease, disorder, or finding
• Prior or concomitant vaccine therapy for COVID-19

Sponsors & Collaborators

• AstraZeneca: lead
• Iqvia Pty Ltd: collaborator

Study Sites (84)

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Phoenix, Arizona, 85018, United States

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Scottsdale, Arizona, 85258, United States

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Little Rock, Arkansas, 72212, United States

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Berkeley, California, 94705, United States

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El Centro, California, 92243, United States

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Los Angeles, California, 90033, United States

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Los Angeles, California, 90095, United States

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San Diego, California, 92103, United States

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San Diego, California, 92134, United States

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San Francisco, California, 94102, United States

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San Francisco, California, 94158, United States

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Torrance, California, 90502, United States

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Denver, Colorado, 80204, United States

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Danbury, Connecticut, 06810, United States

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Coral Gables, Florida, 33134, United States

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Lake Worth, Florida, 33462, United States

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Miami Lakes, Florida, 33016, United States

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Orlando, Florida, 32803, United States

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Honolulu, Hawaii, 96814, United States

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Meridian, Idaho, 83642, United States

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Chicago, Illinois, 60612, United States

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Indianapolis, Indiana, 46202, United States

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Ankeny, Iowa, 50023, United States

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Fairway, Kansas, 66205, United States

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Kansas City, Kansas, 66160, United States

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Wichita, Kansas, 67207, United States

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Wichita, Kansas, 67214, United States

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Lexington, Kentucky, 40509, United States

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Lake Charles, Louisiana, 70601, United States

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Monroe, Louisiana, 71201, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21205, United States

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Bethesda, Maryland, 20889, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02215, United States

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Ann Arbor, Michigan, 48109, United States

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Royal Oak, Michigan, 48073, United States

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Minneapolis, Minnesota, 55425, United States

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Gulfport, Mississippi, 39503, United States

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Butte, Montana, 59701, United States

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Portsmouth, New Hampshire, 03801, United States

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Berlin, New Jersey, 08009, United States

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Albuquerque, New Mexico, 87102, United States

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Brooklyn, New York, 11220, United States

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Mineola, New York, 11501, United States

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New York, New York, 10010, United States

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New York, New York, 10016, United States

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New York, New York, 10032, United States

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Rochester, New York, 14621, United States

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Rochester, New York, 14642, United States

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The Bronx, New York, 10467, United States

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Valhalla, New York, 10595, United States

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Durham, North Carolina, 27710, United States

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Cincinnati, Ohio, 45229, United States

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Columbus, Ohio, 43210, United States

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Yukon, Oklahoma, 73099, United States

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Portland, Oregon, 97239, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Warwick, Rhode Island, 02886, United States

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Charleston, South Carolina, 29425, United States

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North Charleston, South Carolina, 29406, United States

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Spartanburg, South Carolina, 29303, United States

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Knoxville, Tennessee, 37920, United States

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Nashville, Tennessee, 37203, United States

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Austin, Texas, 78745, United States

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Dallas, Texas, 75208, United States

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Fort Sam Houston, Texas, 78234, United States

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Houston, Texas, 77030, United States

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McAllen, Texas, 78504, United States

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San Antonio, Texas, 78236, United States

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Spring, Texas, 77381, United States

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West Jordan, Utah, 84088, United States

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Burlington, Vermont, 05401, United States

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Fort Belvoir, Virginia, 22060, United States

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Richmond, Virginia, 23226, United States

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Seattle, Washington, 98109, United States

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South Charleston, West Virginia, 25309, United States

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Madison, Wisconsin, 53792-5666, United States

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Quillota, 2260000, Chile

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Santiago, 7500539, Chile

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Santiago, 8380453, Chile

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Callao, 0, Peru

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Lima, 15036, Peru

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Lima Cercado, LIMA 1, Peru

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Related Publications (19)

• 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.

  PMID: 32325038 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.

  PMID: 27578435 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.

  PMID: 32007145 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 et al. ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. bioRxiv. 2020;2020.05.13.093195.

  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.

  PMID: 27371814 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.

  PMID: 32015507 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.

  PMID: 15033648 BACKGROUND

• 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.

  PMID: 39225478 DERIVED

• 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.

  PMID: 38643547 DERIVED

• 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.

  PMID: 37385888 DERIVED

• 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.

  PMID: 36713413 DERIVED

• 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.

  PMID: 36610390 DERIVED

• 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.

  PMID: 36106642 DERIVED

• 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.

  PMID: 34587382 DERIVED

Related Links

• Statistical Analysis Plan (SAP)
• D8110C00001-CSP-amendment-6\_Redacted.pdf
• CSR Synopsis

MeSH Terms

Conditions

COVID-19

Interventions

ChAdOx1 nCoV-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vaccines, DNA; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Ann Falsey, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

• Magda Sobieszczyk, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind: two or more parties are unaware of the intervention assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are assigned to one of two or more groups in parallel for the duration of the study.

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 18, 2020
• Study Start: August 28, 2020
• Primary Completion: March 5, 2021
• Study Completion: February 10, 2023
• Last Updated: February 5, 2024
• Results First Posted: April 1, 2022

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

CL (3); PE (3); US (78)