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

A Phase III Randomized, Double-blind, Placebo-controlled, Multi-center Study in Adults to Determine the Safety and Efficacy of AZD7442, a Combination Product of Two Monoclonal Antibodies (AZD8895 and AZD1061), for Post-exposure Prophylaxis of COVID-19

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

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: AZD7442; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1131
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Research Site
  • Hayle, United Kingdom, TR27 5DT
    • Research Site
  • London, United Kingdom, EC1A 7BE
    • Research Site
  • London, United Kingdom, SE5 8AZ
    • Research Site
  • London, United Kingdom, WC1E 6ER
    • Research Site
  • Manchester, United Kingdom, M8 5RB
    • Research Site
  • Southampton, United Kingdom, SO16 6YD
    • Research Site
• United States
  • Alabama
    • Guntersville, Alabama, United States, 35976
      • Research Site
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Research Site
  • California
    • Bakersfield, California, United States, 93309
      • Research Site
    • Corona, California, United States, 92882
      • Research Site
    • Garden Grove, California, United States, 92844
      • Research Site
    • Huntington Beach, California, United States, 92647
      • Research Site
    • Huntington Park, California, United States, 90255
      • Research Site
    • Modesto, California, United States, 95350
      • Research Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Research Site
    • Coral Springs, Florida, United States, 33071
      • Research Site
    • Miami, Florida, United States, 33175
      • Research Site
    • Miami, Florida, United States, 33125
      • Research Site
    • Miami, Florida, United States, 33155
      • Research Site
    • Miami, Florida, United States, 33256
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Miami Lakes, Florida, United States, 33016
      • Research Site
    • Miami Springs, Florida, United States, 33166
      • Research Site
    • Mount Dora, Florida, United States, 32757
      • Research Site
    • North Miami, Florida, United States, 33161
      • Research Site
    • Pembroke Pines, Florida, United States, 33024
      • Research Site
    • Pompano Beach, Florida, United States, 33064
      • Research Site
    • Tampa, Florida, United States, 33603
      • Research Site
    • West Palm Beach, Florida, United States, 33409
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Research Site
    • Buford, Georgia, United States, 30519
      • Research Site
    • Conyers, Georgia, United States, 30094
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Research Site
    • Chicago, Illinois, United States, 60640
      • Research Site
    • Hazel Crest, Illinois, United States, 60429-2196
      • Research Site
  • Indiana
    • Noblesville, Indiana, United States, 46060
      • Research Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Research Site
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Research Site
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Research Site
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Research Site
    • Wilmington, North Carolina, United States, 28401
      • Research Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Research Site
    • El Paso, Texas, United States, 79930
      • Research Site
    • Friendswood, Texas, United States, 77546
      • Research Site
    • Gonzales, Texas, United States, 78629
      • Research Site
    • Harlingen, Texas, United States, 78550
      • Research Site
    • Houston, Texas, United States, 77099
      • Research Site
    • San Antonio, Texas, United States, 78215
      • Research Site
  • Utah
    • Riverton, Utah, United States, 84096
      • Research Site
  • Virginia
    • Alexandria, Virginia, United States, 22311
      • Research Site
    • Portsmouth, Virginia, United States, 23708
      • Research Site
    • Richmond, Virginia, United States, 23226
      • Research Site
  • Washington
    • Tacoma, Washington, United States, 98402
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: AZD7442; Single dose (× 2 IM injections) of 300 mg of AZD7442 on Day 1.; Other Names: A combination of 2 mAbs (AZD8895 and AZD1061)
Placebo Comparator: 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.	Drug: Placebo; Single dose (× 2 IM injections) of saline placebo on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Incidence of ADA to AZD7442 in Serum	457 Days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Iqvia Pty Ltd
• Investigators: Principal Investigator: Myron Levin, MD, AstraZeneca

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: Nature. 2020 Dec;588(7836):E6.
• 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.
• WHO. WHO Coronavirus Disease (COVID-19) Dashboard. 2020a.
• 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.
• 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.
• Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985 Apr-Jun;4(2):213-26. doi: 10.1002/sim.4780040211.
• 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.
• 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.
• 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.

Helpful Links

• redacted CSR Synopsis
• redacted CSP
• redacted SAP

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Actual): April 7, 2021
• Study Completion (Actual): July 25, 2022

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Post exposure COVID-19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Cilgavimab and tixagevimab drug combination
• Other Study ID Numbers: D8850C00003; 2020-004719-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing 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
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes