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

NCT04625972 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: D8850C000032020-004719-28
• Study Type: interventional
• Target: 1,131
• Locations: 2 countries
• Sites: 57

Brief Summary

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

Conditions

COVID-19

Keywords

Post exposure COVID-19

Outcome Measures

Primary Outcomes (2)

• Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness

  To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19

  Planned to be evaluated through Day 183, however, the number of participants required was achieved 127 days after the study start date

• AEs, SAEs, MAAEs, and AESIs Post Dose of IMP

  457 Days

Secondary Outcomes (6)

• The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP

  183 Days

• The Incidence of Participants Who Have a Post-treatment Response (Negative at Baseline to Positive at Any Time Post-baseline) for SARSCoV- 2 Nucleocapsid Antibodies

  366 Days

• The Incidence of COVID-19-related Death Occurring After Dosing With IMP

  366 Days

• The Incidence of All-cause Mortality Occurring After Dosing With IMP

  366 Days

• Serum AZD7442 Concentrations, PK Parameters

  457 Days

Study Arms (2)

AZD7442

EXPERIMENTAL

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.

Drug: AZD7442

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

AZD7442 DRUG

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

Also known as: A combination of 2 mAbs (AZD8895 and AZD1061)

AZD7442

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• History of laboratory-confirmed SARS-CoV-2 infection or SARS-CoV-2 seropositivity at screening.
• History of infection with severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS).
• Known history of allergy or reaction to any component of the study drug formulation.
• Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.
• 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.
• Clinically significant bleeding disorder or prior history of significant bleeding or bruising following IM injections or venipuncture.
• 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.
• 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.
• Currently pregnant or breast feeding.
• Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization.
• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Iqvia Pty Ltd: collaborator

Study Sites (57)

Research Site

Guntersville, Alabama, 35976, United States

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Tempe, Arizona, 85284, United States

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Little Rock, Arkansas, 72205, United States

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Bakersfield, California, 93309, United States

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Corona, California, 92882, United States

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Garden Grove, California, 92844, United States

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Huntington Beach, California, 92647, United States

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Huntington Park, California, 90255, United States

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Modesto, California, 95350, United States

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Coral Gables, Florida, 33134, United States

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Coral Springs, Florida, 33071, United States

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Miami, Florida, 33125, United States

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Miami, Florida, 33155, United States

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Miami, Florida, 33175, United States

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Miami, Florida, 33256, United States

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Miami Lakes, Florida, 33014, United States

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Miami Lakes, Florida, 33016, United States

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Miami Springs, Florida, 33166, United States

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Mt. Dora, Florida, 32757, United States

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North Miami, Florida, 33161, United States

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Pembroke Pines, Florida, 33024, United States

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Pompano Beach, Florida, 33064, United States

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Tampa, Florida, 33603, United States

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West Palm Beach, Florida, 33409, United States

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Atlanta, Georgia, 30328, United States

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Buford, Georgia, 30519, United States

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Conyers, Georgia, 30094, United States

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Chicago, Illinois, 60607, United States

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Chicago, Illinois, 60640, United States

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Hazel Crest, Illinois, 60429-2196, United States

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Noblesville, Indiana, 46060, United States

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West Des Moines, Iowa, 50266, United States

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Wichita, Kansas, 67205, United States

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Owensboro, Kentucky, 42303, United States

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Bethesda, Maryland, 20814, United States

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High Point, North Carolina, 27262, United States

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Wilmington, North Carolina, 28401, United States

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Orangeburg, South Carolina, 29118, United States

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Dallas, Texas, 75235, United States

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El Paso, Texas, 79930, United States

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Friendswood, Texas, 77546, United States

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Gonzales, Texas, 78629, United States

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Harlingen, Texas, 78550, United States

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Houston, Texas, 77099, United States

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San Antonio, Texas, 78215, United States

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Riverton, Utah, 84096, United States

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Alexandria, Virginia, 22311, United States

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Portsmouth, Virginia, 23708, United States

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Richmond, Virginia, 23226, United States

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Tacoma, Washington, 98402, United States

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Bournemouth, BH7 7DW, United Kingdom

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Hayle, TR27 5DT, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, SE5 8AZ, United Kingdom

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London, WC1E 6ER, United Kingdom

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Manchester, M8 5RB, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Related Publications (13)

• 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.

  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.

  PMID: 32123347 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

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

  PMID: 4023479 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/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf. Published 2020b. Accessed 25 September 2020.

  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.

  PMID: 32867706 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

• 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

• 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.

  PMID: 38703336 DERIVED

• 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.

  PMID: 36411267 DERIVED

• 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.

  PMID: 35713300 DERIVED

• 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.

  PMID: 34473343 DERIVED

Related Links

• redacted CSR Synopsis
• redacted CSP
• redacted SAP

MeSH Terms

Conditions

COVID-19

Interventions

cilgavimab and tixagevimab drug combination; tixagevimab; cilgavimab

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

Limitations and Caveats

Results are reported for the Primary analysis conducted during the study.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Myron Levin, MD

  AstraZeneca

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 12, 2020
• Study Start: December 2, 2020
• Primary Completion: April 7, 2021
• Study Completion: July 25, 2022
• Last Updated: November 21, 2023
• Results First Posted: October 25, 2022

Record last verified: 2023-11

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

GB (7); US (50)