Clinical trial NCT04625972: Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: Post exposure COVID-19
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2020-11-12
Enrollment: 1131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness
timeFrame: Planned to be evaluated through Day 183, however, the number of participants required was achieved 127 days after the study start date
measure: AEs, SAEs, MAAEs, and AESIs Post Dose of IMP
timeFrame: 457 Days
Secondary outcomes:
measure: The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP
timeFrame: 183 Days
measure: 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
timeFrame: 366 Days
measure: The Incidence of COVID-19-related Death Occurring After Dosing With IMP
timeFrame: 366 Days
measure: The Incidence of All-cause Mortality Occurring After Dosing With IMP
timeFrame: 366 Days
measure: Serum AZD7442 Concentrations, PK Parameters
timeFrame: 457 Days
measure: Incidence of ADA to AZD7442 in Serum
timeFrame: 457 Days
Other outcomes:
Locations:
city: Guntersville
country: United States
facility: Research Site
state: Alabama
city: Tempe
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Corona
country: United States
facility: Research Site
state: California
city: Garden Grove
country: United States
facility: Research Site
state: California
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: Huntington Park
country: United States
facility: Research Site
state: California
city: Modesto
country: United States
facility: Research Site
state: California
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Coral Springs
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Miami Springs
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Mount Dora
country: United States
facility: Research Site
state: Florida
city: North Miami
country: United States
facility: Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Pompano Beach
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Buford
country: United States
facility: Research Site
state: Georgia
city: Conyers
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Hazel Crest
country: United States
facility: Research Site
state: Illinois
city: Noblesville
country: United States
facility: Research Site
state: Indiana
city: West Des Moines
country: United States
facility: Research Site
state: Iowa
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Owensboro
country: United States
facility: Research Site
state: Kentucky
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: High Point
country: United States
facility: Research Site
state: North Carolina
city: Wilmington
country: United States
facility: Research Site
state: North Carolina
city: Orangeburg
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Friendswood
country: United States
facility: Research Site
state: Texas
city: Gonzales
country: United States
facility: Research Site
state: Texas
city: Harlingen
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Riverton
country: United States
facility: Research Site
state: Utah
city: Alexandria
country: United States
facility: Research Site
state: Virginia
city: Portsmouth
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Bournemouth
country: United Kingdom
facility: Research Site
city: Hayle
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Myron Levin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.
citation: Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985 Apr-Jun;4(2):213-26. doi: 10.1002/sim.4780040211.
citation: WHO. WHO Coronavirus Disease (COVID-19) Dashboard. 2020a.
citation: 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.
citation: 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.
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.
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.
citation: 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.
citation: 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.