Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults

NCT ID: NCT04625972

Last Updated: 2023-11-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1131 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-02

Study Completion Date

2022-07-25

Brief Summary

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This study will assess the efficacy of AZD7442 for the post-exposure prophylaxis of COVID-19 in Adults.

Detailed Description

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SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemic that, as of 29 September 2020, has resulted in a high death toll to date. Unlike the majority of coronaviruses that cause mild disease in humans and animals, SARS-CoV-2 can replicate in the lower respiratory tract to cause acute respiratory distress syndrome and fatal pneumonia. Effective interventions to prevent or treat COVID-19 remain limited in number and clinical experience is limited. Clinical management is limited to supportive care, consequently overwhelming resources of healthcare systems around the world. As a response to the ongoing pandemic, AstraZeneca is developing mAbs to the SARS-CoV-2 S protein. The SARS-CoV-2 spike protein contains the virus's RBD, which enables the virus to bind to receptors on human cells. By targeting this region of the virus's spike protein, antibodies can block the virus's attachment to human cells, and, therefore, is expected to block infection. Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which should prolong their potential prophylactic benefit, and decrease Fc effector function in order to decrease the potential risk of antibody-dependent enhancement of disease. AZD7442, a combination of 2 of these mAbs (AZD8895 and AZD1061), is being evaluated for administration to prevent and/or treat COVID-19. There is currently one ongoing Phase I study with AZD7442.

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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AZD7442

Participants will be randomized in a 2:1 ratio to receive a single dose (× 2 IM injections) of either 300 mg of AZD7442 (n = approximately 750) or saline placebo (n = approximately 375) on Day 1.

Group Type EXPERIMENTAL

AZD7442

Intervention Type DRUG

Single dose (× 2 IM injections) of 300 mg of AZD7442 on Day 1.

Placebo

Participants will be randomized in a 2:1 ratio to receive a single dose (× 2 IM injections) of either 300 mg of AZD7442 (n = approximately 750) or saline placebo (n = approximately 375) on Day 1.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Single dose (× 2 IM injections) of saline placebo on Day 1.

Interventions

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AZD7442

Single dose (× 2 IM injections) of 300 mg of AZD7442 on Day 1.

Intervention Type DRUG

Placebo

Single dose (× 2 IM injections) of saline placebo on Day 1.

Intervention Type DRUG

Other Intervention Names

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A combination of 2 mAbs (AZD8895 and AZD1061)

Eligibility Criteria

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Inclusion Criteria

1. ≥ 18 years of age at the time of signing the informed consent
2. Adults with potential exposure, within 8 days, to a specific identified individual with laboratory-confirmed SARS-COV-2 infection, symptomatic or asymptomatic
3. Participants must not have had COVID-19 symptoms within 10 days of dosing
4. Negative result from point of care SARS-CoV-2 serology test at screening
5. Contraception used by women of childbearing potential, condom by men
6. Able to understand and comply with study requirements/procedures based on the assessment of the investigator

Exclusion Criteria

1. History of laboratory-confirmed SARS-CoV-2 infection or SARS-CoV-2 seropositivity at screening.
2. History of infection with severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS).
3. Known history of allergy or reaction to any component of the study drug formulation.
4. Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.
5. Any prior receipt of investigational or licensed vaccine or other mAb/biologic indicated for the prevention of SARS-CoV-2 or COVID-19 or expected receipt during the period of study follow up.
6. Clinically significant bleeding disorder or prior history of significant bleeding or bruising following IM injections or venipuncture.
7. Any other significant disease, disorder, or finding that, in the judgement of the investigator, may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data.
8. Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study.
9. Currently pregnant or breast feeding.
10. Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization.
11. Employees of the Sponsor involved in planning, executing, supervising, or reviewing the AZD7442 program, clinical study site staff, or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
12. In nations, states, or other jurisdictions that for legal or ethical reasons bar the enrollment of participants who lack capacity to provide their own informed consent, such subjects are excluded.
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Iqvia Pty Ltd

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Myron Levin, MD

Role: PRINCIPAL_INVESTIGATOR

AstraZeneca

Locations

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Research Site

Guntersville, Alabama, United States

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Tempe, Arizona, United States

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Little Rock, Arkansas, United States

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Bakersfield, California, United States

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Corona, California, United States

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Garden Grove, California, United States

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Huntington Beach, California, United States

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Huntington Park, California, United States

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Modesto, California, United States

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Coral Gables, Florida, United States

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Coral Springs, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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Miami Lakes, Florida, United States

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Miami Springs, Florida, United States

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Mt. Dora, Florida, United States

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North Miami, Florida, United States

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Pembroke Pines, Florida, United States

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Pompano Beach, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Atlanta, Georgia, United States

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Buford, Georgia, United States

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Conyers, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Hazel Crest, Illinois, United States

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Noblesville, Indiana, United States

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West Des Moines, Iowa, United States

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Wichita, Kansas, United States

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Owensboro, Kentucky, United States

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Bethesda, Maryland, United States

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High Point, North Carolina, United States

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Wilmington, North Carolina, United States

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Orangeburg, South Carolina, United States

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Dallas, Texas, United States

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El Paso, Texas, United States

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Friendswood, Texas, United States

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Gonzales, Texas, United States

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Harlingen, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Riverton, Utah, United States

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Alexandria, Virginia, United States

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Portsmouth, Virginia, United States

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Richmond, Virginia, United States

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Tacoma, Washington, United States

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Bournemouth, , United Kingdom

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Hayle, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Southampton, , United Kingdom

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Countries

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United States United Kingdom

References

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CDC. (Centers for Disease Control and Prevention). Coronavirus Disease 2019 (COVID-19), Symptoms of Coronavrus. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Published 2020. Accessed 01 July 2020.

Reference Type 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.

Reference Type BACKGROUND
PMID: 32123347 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27578435 (View on PubMed)

Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985 Apr-Jun;4(2):213-26. doi: 10.1002/sim.4780040211.

Reference Type BACKGROUND
PMID: 4023479 (View on PubMed)

WHO. WHO Coronavirus Disease (COVID-19) Dashboard. 2020a.

Reference Type BACKGROUND

WHO. WHO R&D Blueprint COVID-19 Therapeutic Trial Synopsis Draft 18 February 2020. https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf. Published 2020b. Accessed 25 September 2020.

Reference Type BACKGROUND

Xie Y, Wang Z, Liao H, Marley G, Wu D, Tang W. Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: systematic review and meta-analysis. BMC Infect Dis. 2020 Aug 31;20(1):640. doi: 10.1186/s12879-020-05371-2.

Reference Type BACKGROUND
PMID: 32867706 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32015507 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15033648 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38703336 (View on PubMed)

Levin MJ, Ustianowski A, Thomas S, Templeton A, Yuan Y, Seegobin S, Houlihan CF, Menendez-Perez I, Pollett S, Arends RH, Beavon R, Dey K, Garbes P, Kelly EJ, Koh GCKW, Ivanov S, Near KA, Sharbaugh A, Streicher K, Pangalos MN, Esser MT; COVID-19 Study to Optimally Reduce Morbidity in CareHomes and Sites with Enhanced Risk (STORMCHASER) Study Group. AZD7442 (Tixagevimab/Cilgavimab) for Post-Exposure Prophylaxis of Symptomatic Coronavirus Disease 2019. Clin Infect Dis. 2023 Apr 3;76(7):1247-1256. doi: 10.1093/cid/ciac899.

Reference Type DERIVED
PMID: 36411267 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35713300 (View on PubMed)

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Reference Type DERIVED
PMID: 34473343 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-004719-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D8850C00003

Identifier Type: -

Identifier Source: org_study_id

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