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

COVID-19 Clinical Trial

— STORM CHASER  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04625972
• Other study ID #: D8850C00003
• Secondary ID: 2020-004719-28
• Status: Completed
• Phase: Phase 3
• Start date: December 2, 2020
• Est. completion date: July 25, 2022

Study information

• Verified date: November 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1131
• Est. completion date: July 25, 2022
• Est. primary completion date: April 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• AZD7442
Single dose (× 2 IM injections) of 300 mg of AZD7442 on Day 1.
• Placebo
Single dose (× 2 IM injections) of saline placebo on Day 1.

Locations

Country	Name	City	State
United Kingdom	Research Site	Bournemouth
United Kingdom	Research Site	Hayle
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Southampton
United States	Research Site	Alexandria	Virginia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Bakersfield	California
United States	Research Site	Bethesda	Maryland
United States	Research Site	Buford	Georgia
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Conyers	Georgia
United States	Research Site	Coral Gables	Florida
United States	Research Site	Coral Springs	Florida
United States	Research Site	Corona	California
United States	Research Site	Dallas	Texas
United States	Research Site	El Paso	Texas
United States	Research Site	Friendswood	Texas
United States	Research Site	Garden Grove	California
United States	Research Site	Gonzales	Texas
United States	Research Site	Guntersville	Alabama
United States	Research Site	Harlingen	Texas
United States	Research Site	Hazel Crest	Illinois
United States	Research Site	High Point	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntington Park	California
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Miami Springs	Florida
United States	Research Site	Modesto	California
United States	Research Site	Mount Dora	Florida
United States	Research Site	Noblesville	Indiana
United States	Research Site	North Miami	Florida
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Owensboro	Kentucky
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Pompano Beach	Florida
United States	Research Site	Portsmouth	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Riverton	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	Tacoma	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Tempe	Arizona
United States	Research Site	West Des Moines	Iowa
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Wichita	Kansas
United States	Research Site	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Iqvia Pty Ltd

Countries where clinical trial is conducted

United States,  United Kingdom, 

References & Publications (9)

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.

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. — View Citation

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. — View Citation

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

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

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	AEs, SAEs, MAAEs, and AESIs Post Dose of IMP		457 Days
Secondary	The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP		183 Days
Secondary	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
Secondary	The Incidence of COVID-19-related Death Occurring After Dosing With IMP		366 Days
Secondary	The Incidence of All-cause Mortality Occurring After Dosing With IMP		366 Days
Secondary	Serum AZD7442 Concentrations, PK Parameters		457 Days
Secondary	Incidence of ADA to AZD7442 in Serum		457 Days

External Links

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•   redacted CSR Synopsis
•   redacted SAP