Clinical trial NCT04516746: Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults
Official title: A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults, to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
SARS-CoV-2
Keywords: COVID-19 Vaccine
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2020-08-18
Enrollment: 32450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are assigned to one of two or more groups in parallel for the duration of the study.
Primary purpose: TREATMENT

Brief summary: The aim of the study is to assess the safety, efficacy, and immunogenicity of AZD1222 for the prevention of COVID-19.

Detailed description: The COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. Currently, there are no specific treatments available against COVID-19 and accelerated vaccine development is urgently needed. A safe and effective vaccine for COVID-19 prevention would have significant public health impact.

Eligibility criteria: Inclusion Criteria:

* Increased risk of SARS-CoV-2 infection
* Medically stable

Exclusion Criteria:

* confirmed or suspected immunosuppressive or immunodeficient state
* significant disease, disorder, or finding
* Prior or concomitant vaccine therapy for COVID-19

Primary outcomes:
measure: Number of Participants With Binary Response
timeFrame: From 15 days post second dose up to data cut-off date (DCO) of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Number of Participants With Adverse Events (AEs) Post Each Dose of Study Intervention
timeFrame: From Day 1 up to 28 days post second dose of study intervention, approximately 57 days
measure: Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Prior to Non-study COVID-19 Vaccination
timeFrame: From Day 1 up to receipt of non-study COVID-19 vaccination or a maximum of Day 760 for participants without non-study COVID-19 vaccination.
measure: Number of Participants With Local and Systemic Solicited AEs in the Substudy Only
timeFrame: From Day 1 up to 7 days post each dose of study intervention, approximately 14 days
Secondary outcomes:
measure: Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Post Second Dose of Study Intervention
timeFrame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Number of Participants With First COVID-19 Symptomatic Illness Using Centers for Disease Control and Prevention (CDC) Criteria Post Second Dose of Study Intervention
timeFrame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Post Second Dose of Study Intervention
timeFrame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Post Second Dose of Study Intervention
timeFrame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post Second Dose of Study Intervention
timeFrame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Post First Dose of Study Intervention
timeFrame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Number of Participants With COVID-19-Related Emergency Department Visits Post Second Dose of Study Intervention
timeFrame: From 15 days post second dose up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of 17 weeks
measure: Geometric Mean Titers (GMTs) for SARS-CoV-2 Spike (S) and Receptor Binding Domain (RBD) Antibodies as Measured by Meso Scale Discovery (MSD) Serology Assay
timeFrame: Baseline (Day 1) and Days 15, 29, 43, 57, 90, 180, 360, and 730
measure: Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
timeFrame: Days 15, 29, 43, 57, 90, 180, 360, and 730
measure: Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay
timeFrame: Days 15, 29, 43, 57, 90, 180, 360, and 730
measure: GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay
timeFrame: Baseline (Day 1) and Days 15, 29, 43, 57, 90, 180, and 360
measure: GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay
timeFrame: Days 15, 29, 43, 57, 90, 180, and 360
measure: Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay
timeFrame: Days 15, 29, 43, 57, 90, 180, and 360
measure: Number of Participants With COVID-19 Symptomatic Illness Post First Dose of Study Intervention
timeFrame: From Day 1 up to DCO of 05 March 2021 or study discontinuation or unblinding or receipt of non-study COVID-19 vaccination, up to a maximum of approximately 27 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Berkeley
country: United States
facility: Research Site
state: California
city: El Centro
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Danbury
country: United States
facility: Research Site
state: Connecticut
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Lake Worth
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Meridian
country: United States
facility: Research Site
state: Idaho
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Ankeny
country: United States
facility: Research Site
state: Iowa
city: Fairway
country: United States
facility: Research Site
state: Kansas
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Lake Charles
country: United States
facility: Research Site
state: Louisiana
city: Monroe
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Royal Oak
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Gulfport
country: United States
facility: Research Site
state: Mississippi
city: Butte
country: United States
facility: Research Site
state: Montana
city: Portsmouth
country: United States
facility: Research Site
state: New Hampshire
city: Berlin
country: United States
facility: Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Bronx
country: United States
facility: Research Site
state: New York
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Mineola
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Valhalla
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Yukon
country: United States
facility: Research Site
state: Oklahoma
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Warwick
country: United States
facility: Research Site
state: Rhode Island
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: North Charleston
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Fort Sam Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: McAllen
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Spring
country: United States
facility: Research Site
state: Texas
city: West Jordan
country: United States
facility: Research Site
state: Utah
city: Burlington
country: United States
facility: Research Site
state: Vermont
city: Fort Belvoir
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: South Charleston
country: United States
facility: Research Site
state: West Virginia
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Quillota
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Callao
country: Peru
facility: Research Site
city: Cercado De Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
Study officials:
affiliation: University of Rochester
name: Ann Falsey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Magda Sobieszczyk, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Clinical Study Protocol - 1.0 AstraZeneca AZD1222 - D8110C00001 CONFIDENTIAL AND PROPRIETARY 92 of 92
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citation: Sobieszczyk ME, Maaske J, Falsey AR, Sproule S, Robb ML, Frenck RW Jr, Tieu HV, Mayer KH, Corey L, Neuzil KM, Tong T, Brewinski Isaacs M, Janes H, Bansal H, Edwards LM, Green JA, Kelly EJ, Shoemaker K, Takas T, White T, Bhuyan P, Villafana T, Hirsch AI; AstraZeneca AZD1222 Clinical Study Group. Durability of protection and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine over 6 months. J Clin Invest. 2022 Sep 15;132(18):e160565. doi: 10.1172/JCI160565.
citation: Falsey AR, Sobieszczyk ME, Hirsch I, Sproule S, Robb ML, Corey L, Neuzil KM, Hahn W, Hunt J, Mulligan MJ, McEvoy C, DeJesus E, Hassman M, Little SJ, Pahud BA, Durbin A, Pickrell P, Daar ES, Bush L, Solis J, Carr QO, Oyedele T, Buchbinder S, Cowden J, Vargas SL, Guerreros Benavides A, Call R, Keefer MC, Kirkpatrick BD, Pullman J, Tong T, Brewinski Isaacs M, Benkeser D, Janes HE, Nason MC, Green JA, Kelly EJ, Maaske J, Mueller N, Shoemaker K, Takas T, Marshall RP, Pangalos MN, Villafana T, Gonzalez-Lopez A; AstraZeneca AZD1222 Clinical Study Group. Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine. N Engl J Med. 2021 Dec 16;385(25):2348-2360. doi: 10.1056/NEJMoa2105290. Epub 2021 Sep 29.