Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults

NCT04723394 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: D8851C00001
• Study Type: interventional
• Target: 910
• Locations: 15 countries
• Sites: 103

Brief Summary

This Phase III study will assess whether AZD7442 (a combination of 2 mAbs) can safely treat outpatient adults with COVID-19 and prevent either severe COVID-19 or death.

Conditions

COVID-19

Keywords

Treatment of COVID-19

Outcome Measures

Primary Outcomes (1)

• A Composite of Either Severe COVID-19 or Death From Any Cause Through Day 29

  Severe COVID-19 is characterized by a minimum of either pneumonia (fever, cough, tachypnea, or dyspnea, and lung infiltrates) or hypoxemia (SpO2 \< 90% in room air and/or severe respiratory distress) and a WHO Clinical Progression Scale score of 5 or higher.

  Baseline (Day 1) and Day 29

Secondary Outcomes (1)

• A Composite of Death From Any Cause or Hospitalization for COVID-19 Complications or Sequelae Through Day 169

  Baseline (Day 1) and Day 169

Study Arms (2)

AZD7442

EXPERIMENTAL

Up to approximately 1700 participants will be randomized in a 1:1 ratio. Arm 1 (n=up to approximately 850) will receive a single dose (× 2 IM injections) of 600 mg of AZD7442.

Drug: AZD7442

Placebo

PLACEBO COMPARATOR

Up to approximately 1700 participants will be randomized in a 1:1 ratio. Arm 2 (n=up to approximately 850) will receive saline placebo.

Drug: Placebo

Interventions

AZD7442 DRUG

Single dose (× 2 separate IM injections) of 600 mg of AZD7442 or saline placebo on Day 1.

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

AZD7442

Placebo DRUG

Single dose (× 2 separate IM injections) of 600 mg of AZD7442 or saline placebo on Day 1.

Placebo

Eligibility Criteria

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

You may qualify if:

• Participant has a documented laboratory-confirmed SARS-CoV-2 infection, as determined by a molecular test (antigen or nucleic acid) from any respiratory tract specimen (eg, oropharyngeal, NP, or nasal swab, or saliva) collected ≤ 3 days prior to Day 1.
• WHO Clinical Progression Scale score \> 1 and \< 4.
• Participant must be dosed with IMP no more than 7 days from self-reported onset of COVID-19-related symptoms (mild to moderate COVID-19) or measured fever, defined as the self-reported date of first reported sign/symptom.
• One or more of the following signs/symptoms must be present within 24 hours prior to Day1: Cough, Sore throat, Shortness of breath or difficulty breathing at rest or with activity, Body pain or muscle pain/aches, Fatigue, Headache, Chills, Nasal obstruction or congestion, Nasal discharge, Nausea or vomiting, Diarrhea, New loss of taste or smell.
• Oxygenation saturation of ≥ 92% obtained at rest by study staff within 24 hours prior to Day 1 (unless participant regularly receives chronic supplementary oxygen for an underlying lung condition).
• Participant agrees not to participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period until reaching hospitalization or 28 days after entry into the study (whichever is earliest).
• Participant must be ≥ 18 years of age, provide informed consent and is able to comply with study requirements/procedures.
• Male participants: Contraception for male participants is not required; however, to avoid the transfer of any fluids, all male participants must use a condom from Day 1 and agree to continue through 90 days following administration of IMP.
• Women of childbearing potential must use one highly effective form of birth control.

You may not qualify if:

• History or current hospitalization for COVID-19.
• Current need for hospitalization/immediate medical attention in a clinic/emergency room service
• Previous hypersensitivity, infusion related reaction, or adverse reaction to any monoclonal antibodies or known allergy to components of the IMP or placebo.
• Receipt of any investigational or licensed vaccine for prevention of COVID-19 at any time prior to entry into this study or expected administration immediately after enrollment.
• Current requirement or anticipated impending need for mechanical ventilation.
• Any significant disease, disorder or finding that may increase risk to the participant that might affect his/her ability to participate in this study.
• Received convalescent COVID-19 plasma treatment any time prior to entry into this study.
• Receipt of systemic steroids (e.g., prednisone, dexamethasone) or inhaled steroids within 30 days prior to study entry, unless a stable dose is used for a chronic condition.
• Receipt of any IMP in the previous 90 days or 5 half lives (whichever is longer), or expected receipt of IMP during the study follow-up period, or concurrent participation in another interventional study.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (103)

Research Site

Jasper, Alabama, 35501, United States

Location

Research Site

Tucson, Arizona, 85704, United States

Location

Research Site

Long Beach, California, 90806, United States

Location

Research Site

Northridge, California, 91324, United States

Location

Research Site

Cutler Bay, Florida, 33157, United States

Location

Research Site

Miami, Florida, 33125, United States

Location

Research Site

Miami, Florida, 33165, United States

Location

Research Site

Pompano Beach, Florida, 33064, United States

Location

Research Site

Chicago, Illinois, 60621, United States

Location

Research Site

Lake Charles, Louisiana, 70601, United States

Location

Research Site

St Louis, Missouri, 63141, United States

Location

Research Site

La Vista, Nebraska, 68128, United States

Location

Research Site

New York, New York, 10016, United States

Location

Research Site

Charlotte, North Carolina, 28208, United States

Location

Research Site

Charlotte, North Carolina, 28277, United States

Location

Research Site

Statesville, North Carolina, 28625, United States

Location

Research Site

Fargo, North Dakota, 58104, United States

Location

Research Site

Columbus, Ohio, 43213, United States

Location

Research Site

West Columbia, South Carolina, 29169, United States

Location

Research Site

Dallas, Texas, 75235, United States

Location

Research Site

Houston, Texas, 77027, United States

Location

Research Site

Houston, Texas, 77057, United States

Location

Research Site

Houston, Texas, 77093, United States

Location

Research Site

Humble, Texas, 77338, United States

Location

Research Site

Buenos Aires, B7600FYW, Argentina

Location

Research Site

Buenos Aires, C1039, Argentina

Location

Research Site

Buenos Aires, C1430EGF, Argentina

Location

Research Site

Munro, B1605FRE, Argentina

Location

Research Site

Blumenau, 89030-101, Brazil

Location

Research Site

Porto Alegre, 90430-001, Brazil

Location

Research Site

Ribeirão Preto, 14051-140, Brazil

Location

Research Site

São Paulo, 01228-200, Brazil

Location

Research Site

Sorocaba, 18040-425, Brazil

Location

Research Site

Hradec Králové, 500 02, Czechia

Location

Research Site

Kolín, 280 02, Czechia

Location

Research Site

Svitavy, 568 25, Czechia

Location

Research Site

Berlin, 10439, Germany

Location

Research Site

Berlin, 10777, Germany

Location

Research Site

Cologne, 50668, Germany

Location

Research Site

Frankfurt, 60596, Germany

Location

Research Site

Frankfurt am Main, 60389, Germany

Location

Research Site

Friedrichshain, 10243, Germany

Location

Research Site

Hamburg, 20095, Germany

Location

Research Site

Hanover, 30625, Germany

Location

Research Site

Koblenz, 56068, Germany

Location

Research Site

Mainz, 55128, Germany

Location

Research Site

München, 80336, Germany

Location

Research Site

München-Pasing, 81241, Germany

Location

Research Site

Debrecen, 4031, Hungary

Location

Research Site

Gyöngyös, 3200, Hungary

Location

Research Site

Guastalla, 42016, Italy

Location

Research Site

Milan, 20127, Italy

Location

Research Site

Piacenza, 29121, Italy

Location

Research Site

Pisa, 56124, Italy

Location

Research Site

Roma, 00149, Italy

Location

Research Site

Chiba, 260-0852, Japan

Location

Research Site

Hachioji-shi, 193-0998, Japan

Location

Research Site

Iruma-Gun, 350-0495, Japan

Location

Research Site

Kyoto, 607-8062, Japan

Location

Research Site

Maebashi, 371-0811, Japan

Location

Research Site

Narita-shi, 286-8520, Japan

Location

Research Site

Sendai, 983-8512, Japan

Location

Research Site

Shinagawa-ku, 140-8522, Japan

Location

Research Site

Shinagawa-ku, 142-8666, Japan

Location

Research Site

Shinjuku-ku, 162-8655, Japan

Location

Research Site

Chihuahua City, 31350, Mexico

Location

Research Site

Cuauhtémoc, 06700, Mexico

Location

Research Site

Cuautitlán Izcalli, 54750, Mexico

Location

Research Site

Ecatepec de Morelos, 55450, Mexico

Location

Research Site

Guadalajara, 44100, Mexico

Location

Research Site

Guadalajara, 44200, Mexico

Location

Research Site

Mazatlán, 82110, Mexico

Location

Research Site

Mérida, 97070, Mexico

Location

Research Site

Monterrey, 64460, Mexico

Location

Research Site

Tlalpan, 14050, Mexico

Location

Research Site

Tlalpan, 14080, Mexico

Location

Research Site

Lima, 15088, Peru

Location

Research Site

Rzeszów, 35-326, Poland

Location

Research Site

Wołomin, 05-200, Poland

Location

Research Site

Moscow, 143442, Russia

Location

Research Site

Murmansk, 183047, Russia

Location

Research Site

Saint Petersburg, 192283, Russia

Location

Research Site

Saint Petersburg, 196084, Russia

Location

Research Site

Saint Petersburg, 197227, Russia

Location

Research Site

Saint Petersburg, 199106, Russia

Location

Research Site

Saint Petersburg, 199226, Russia

Location

Research Site

Cabra, 14940, Spain

Location

Research Site

Centelles (Barcelona), 08540, Spain

Location

Research Site

Girona, 17005, Spain

Location

Research Site

Madrid, 28031, Spain

Location

Research Site

Málaga, 29010, Spain

Location

Research Site

Dnipro, 49102, Ukraine

Location

Research Site

Ivano-Frankivsk, 78018, Ukraine

Location

Research Site

Kherson, 73000, Ukraine

Location

Research Site

Blackpool, FY3 7EN, United Kingdom

Location

Research Site

Bracknell, RG12 8WY, United Kingdom

Location

Research Site

Bristol, BS8 2PU, United Kingdom

Location

Research Site

Cambridge, CB2 2QQ, United Kingdom

Location

Research Site

Connor Downs, TR27 5DT, United Kingdom

Location

Research Site

Highgate, N19 5NF, United Kingdom

Location

Research Site

Leicester, LE5 4LJ, United Kingdom

Location

Research Site

Preston, PR2 9HT, United Kingdom

Location

Research Site

Rochdale, OL11 4AU, United Kingdom

Location

Related Publications (19)

• Ashraf-Kashani and Kumar 2017 Ashraf-Kashani N, Kumar R. High-flow nasal oxygen therapy. BJA Education. 2017;17:57-62.

  BACKGROUND

• Gou and Xi 2019 Gou J, Xi D. Hierarchical testing of a primary and a secondary endpoint in a group sequential design with different information times. Statistics in Biopharmaceutical Research. 2019;11(4):398-406, DOI: 10.1080/19466315.2018.1546613.

  BACKGROUND

• ICMRA 2020 International Coalition of Medicines Regulatory Authorities. Global regulatory workshop on COVID-19 therapeutics: agreement on acceptable endpoints for clinical trials. Published online July 2020. Retrieved from http://icmra.info/drupal/news/20july2020/summary

  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

• Sharma S, Danckers M, Sanghavi DK, Chakraborty RK. High-Flow Nasal Cannula. 2023 Apr 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK526071/

  PMID: 30252327 BACKGROUND

• Tamhane AC, Mehta CR, Liu L. Testing a primary and a secondary endpoint in a group sequential design. Biometrics. 2010 Dec;66(4):1174-84. doi: 10.1111/j.1541-0420.2010.01402.x.

  PMID: 20337631 BACKGROUND

• WHO 2020 WHO COVID-19 Dashboard. Available from: https://covid19.who.int

  BACKGROUND

• WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. doi: 10.1016/S1473-3099(20)30483-7. Epub 2020 Jun 12.

  PMID: 32539990 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

• CDC, 2021 CDC, Investigating the Impact of COVID-19 during Pregnancy, available from https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19/what-cdc-is-doing.html

  BACKGROUND

• CDC, Growth Charts CDC, Growth Charts, available from https://www.cdc.gov/growthcharts/clinical_charts.htm

  BACKGROUND

• Lilly BLAZE-1 2021 Lilly. Lilly's bamlanivimab and etesevimab together reduced hospitalizations and death in Phase 3 trial for early COVID-19. Published online 10 March 2021. Accessed 31 March 2021. https://investor.lilly.com/news-releases/news-release-details/lillys-bamlanivimab-and-etesevimab-together-reduced

  BACKGROUND

• Regeneron Pharmaceuticals, Inc. REGEN-COV Outpatient Trial 2021 Regeneron Pharmaceuticals, Inc. Phase 3 trial shows Regen-Cov™ (casirivimab with imdevimab) antibody cocktail reduced hospitalization or death by 70% in non-hospitalized Covid-19 patients. Published online 23 March 2021. Accessed 31 March 2021. https://investor.regeneron.com/news-releases/news-release-details/phase-3-trial-shows-regen-covtm-casirivimab-imdevimab-antibody#:~:text=This%20definitive%20Phase%203%20outcomes,71%25%20(2%2C400%20mg%20IV)

  BACKGROUND

• Hobbs FDR, Montgomery H, Padilla F, Simon-Campos JA, Arbetter D, Seegobin S, Kiazand A, Streicher K, Martinez-Alier N, Cohen TS, Esser MT. Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial. Infect Dis Ther. 2024 Mar;13(3):521-533. doi: 10.1007/s40121-024-00931-4. Epub 2024 Feb 25.

  PMID: 38403865 DERIVED

• Hobbs FDR, Montgomery H, Padilla F, Simon-Campos JA, Kim K, Arbetter D, Padilla KW, Reddy VP, Seegobin S, Streicher K, Templeton A, Viani RM, Johnsson E, Koh GCKW, Esser MT. Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial. Infect Dis Ther. 2023 Sep;12(9):2269-2287. doi: 10.1007/s40121-023-00861-7. Epub 2023 Sep 26.

  PMID: 37751015 DERIVED

• Montgomery H, Hobbs FDR, Padilla F, Arbetter D, Templeton A, Seegobin S, Kim K, Campos JAS, Arends RH, Brodek BH, Brooks D, Garbes P, Jimenez J, Koh GCKW, Padilla KW, Streicher K, Viani RM, Alagappan V, Pangalos MN, Esser MT; TACKLE study group. Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2022 Oct;10(10):985-996. doi: 10.1016/S2213-2600(22)00180-1. Epub 2022 Jun 7.

  PMID: 35688164 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 CSP
• Redacted SAP
• Redacted CSR Synopsis

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

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: January 25, 2021
• Study Start: January 28, 2021
• Primary Completion: August 21, 2021
• Study Completion: October 19, 2022
• Last Updated: July 5, 2023
• Results First Posted: December 20, 2022

Record last verified: 2023-06

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

PL (2); ME (11); JP (10); CZ (3); RU (7); US (24); PE (1); AR (4); UA (3); IT (5); ES (5); DE (12); HU (2); BR (5); GB (9)