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Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04516746
Recruitment Status : Active, not recruiting
First Posted : August 18, 2020
Results First Posted : April 1, 2022
Last Update Posted : July 21, 2022
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions COVID-19
SARS-CoV-2
Interventions Biological: AZD1222
Biological: Placebo
Enrollment 32459
Recruitment Details A total of 88 centers across 3 countries in the United States of America, Chile and Peru randomized adult participants who were healthy or had medically stable chronic diseases and were at increased risk for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) acquisition and coronavirus disease-2019 (COVID-19) in this study. First participant was randomized on 28 August 2020 and clinical data cut-off (DCO) date was 05 March 2021. Final analysis results will be reported at a later date.
Pre-assignment Details The study had a screening period (14 days), followed by a treatment and follow-up period (up to 760 days). A total of 32451 participants were randomized in a 2:1 ratio to receive AZD1222 or placebo. The first participants randomized in each age group in the United States of America participated in a substudy to assess immunogenicity and reactogenicity.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description Participants were randomized to receive 2 intramuscular (IM) doses of either 5*10^10 viral particles (vp) (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29. Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Period Title: Overall Study
Started [1] 21635 10816
Participants Who Received First Dose 21583 10796
Participants Who Received Second Dose 20769 9951
Completed 0 0
Not Completed 21635 10816
Reason Not Completed
Ongoing in the study at clinical DCO for the primary analysis.             21090             10305
Withdrawal by Subject             362             408
Lost to Follow-up             157             86
Protocol deviation             18             7
Death             8             7
Physician Decision             0             2
Other             0             1
[1]
Participants randomized.
Arm/Group Title AZD1222 Placebo Total
Hide Arm/Group Description Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29. Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29. Total of all reporting groups
Overall Number of Baseline Participants 17662 8550 26212
Hide Baseline Analysis Population Description
The fully vaccinated analysis set (FVS) included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR)-positive confirmed COVID-19 infection.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17662 participants 8550 participants 26212 participants
49.8  (15.73) 49.9  (15.71) 49.9  (15.73)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17662 participants 8550 participants 26212 participants
Female
7740
  43.8%
3721
  43.5%
11461
  43.7%
Male
9922
  56.2%
4829
  56.5%
14751
  56.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17662 participants 8550 participants 26212 participants
Hispanic or Latino
4035
  22.8%
2064
  24.1%
6099
  23.3%
Not Hispanic or Latino
13351
  75.6%
6370
  74.5%
19721
  75.2%
Not reported
238
   1.3%
106
   1.2%
344
   1.3%
Unknown
38
   0.2%
10
   0.1%
48
   0.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17662 participants 8550 participants 26212 participants
Multiple
421
   2.4%
202
   2.4%
623
   2.4%
White
14011
  79.3%
6755
  79.0%
20766
  79.2%
Black or African American
1401
   7.9%
706
   8.3%
2107
   8.0%
Asian
747
   4.2%
352
   4.1%
1099
   4.2%
American Indian or Alaska Native
744
   4.2%
373
   4.4%
1117
   4.3%
Native Hawaiian or Other Pacific Islander
50
   0.3%
14
   0.2%
64
   0.2%
Not reported
207
   1.2%
110
   1.3%
317
   1.2%
Unknown
81
   0.5%
38
   0.4%
119
   0.5%
1.Primary Outcome
Title Number of Participants Achieving Binary Response
Hide Description A binary response, whereby a participant with negative serostatus at baseline is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case. The primary efficacy analysis was performed once approximately 150 events meeting the primary efficacy outcome measure definition had occurred across the AZD1222 and placebo groups.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FVS included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 17662 8550
Measure Type: Count of Participants
Unit of Measure: Participants
73
   0.4%
130
   1.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% confidence interval (CI) and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor [age group at informed consent] as covariates, and log of the follow up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression with robust variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 73.98
Confidence Interval (2-Sided) 95%
65.34 to 80.47
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Adverse Events (AEs) Occurring Post Each Dose of Study Intervention
Hide Description An AE is the development of any untoward medical occurrence in a clinical study participant administered medicinal product and which does not necessarily have a causal relationship with this medicinal product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame From Day 1 up to 28 days post second dose of study intervention, approximately 57 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least one dose of study intervention.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 21587 10792
Measure Type: Count of Participants
Unit of Measure: Participants
After first dose Number Analyzed 21587 participants 10792 participants
5736
  26.6%
1926
  17.8%
After second dose Number Analyzed 20773 participants 9947 participants
5074
  24.4%
1797
  18.1%
After any dose Number Analyzed 21587 participants 10792 participants
8771
  40.6%
3201
  29.7%
3.Primary Outcome
Title Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Occurring Throughout the Study
Hide Description An SAE is an AE occurring during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. AESIs were events of scientific and medical interest specific to the further understanding of the study intervention safety profile and required close monitoring and rapid communication by the investigators to the sponsor. MAAEs are defined as AEs leading to medically-attended visits that were not routine visits for physical examination or vaccination, such as an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least one dose of study intervention.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 21587 10792
Measure Type: Count of Participants
Unit of Measure: Participants
SAEs
140
   0.6%
78
   0.7%
MAAEs
1617
   7.5%
815
   7.6%
AESIs
525
   2.4%
416
   3.9%
4.Primary Outcome
Title Number of Participants With Local and Systemic Solicited AEs in the Substudy Only
Hide Description Solicited AEs are local or systemic predefined events for assessment of reactogenicity. Solicited AEs were collected in a e-Diary only for participants in the substudy.
Time Frame From Day 1 up to 7 days post each dose of study intervention, approximately 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least one dose of study intervention. Only participants included in the substudy were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 2037 1013
Measure Type: Count of Participants
Unit of Measure: Participants
Solicited local AEs: After first dose Number Analyzed 1830 participants 920 participants
1250
  68.3%
173
  18.8%
Solicited local AEs: After second dose Number Analyzed 1829 participants 908 participants
977
  53.4%
120
  13.2%
Solicited local AEs: After any dose Number Analyzed 1944 participants 979 participants
1440
  74.1%
239
  24.4%
Solicited systemic AEs: After first dose Number Analyzed 1842 participants 924 participants
1191
  64.7%
415
  44.9%
Solicited systemic AEs: After second dose Number Analyzed 1821 participants 905 participants
862
  47.3%
314
  34.7%
Solicited systemic AEs: After any dose Number Analyzed 1947 participants 980 participants
1395
  71.6%
519
  53.0%
5.Secondary Outcome
Title Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Occurring Post Second Dose of Study Intervention
Hide Description The incidence of the first post-intervention response (negative at baseline to positive post intervention with study intervention) for SARS-CoV-2 nucleocapsid antibodies occurring ≥ 15 days post second dose of study intervention (key secondary endpoint).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FVS included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 17662 8550
Measure Type: Count of Participants
Unit of Measure: Participants
156
   0.9%
202
   2.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor [age group at informed consent] as covariates, and log of the follow up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression with robust variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 64.32
Confidence Interval (2-Sided) 95%
56.05 to 71.03
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With First COVID-19 Symptomatic Illness Using Centers for Disease Control and Prevention (CDC) Criteria Occurring Post Second Dose of Study Intervention
Hide Description The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using CDC criteria. Participant must present with at least one of the following symptoms per CDC criteria: fever, shortness of breath, difficulty breathing, chills, cough, fatigue, muscle aches, body aches, headache, new loss of taste, new loss of smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhea.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FVS included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 17662 8550
Measure Type: Count of Participants
Unit of Measure: Participants
95
   0.5%
145
   1.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor [age group at informed consent] as covariates, and log of the follow up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression with robust variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 69.65
Confidence Interval (2-Sided) 95%
60.68 to 76.57
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Occurring Post Second Dose of Study Intervention
Hide Description The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using University of Oxford-defined symptom criteria: new onset of fever (> 100 °Fahrenheit [> 37.8 °Celsius]), cough, shortness of breath, or anosmia/ageusia.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FVS included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 17662 8550
Measure Type: Count of Participants
Unit of Measure: Participants
86
   0.5%
136
   1.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor [age group at informed consent] as covariates, and log of the follow up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression with robust variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 70.70
Confidence Interval (2-Sided) 95%
61.62 to 77.64
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Occurring Post Second Dose of Study Intervention
Hide Description The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention regardless of evidence of prior SARS-CoV-2 infection (key secondary endpoint).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FVS regardless of prior SARS-COV-2 infection included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 18563 9031
Measure Type: Count of Participants
Unit of Measure: Participants
76
   0.4%
135
   1.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor [age group at informed consent] as covariates, and log of the follow up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression with robust variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 73.68
Confidence Interval (2-Sided) 95%
65.13 to 80.13
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Occurring Post Second Dose of Study Intervention
Hide Description The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring ≥ 15 days post second dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death (key secondary endpoint).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FVS included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 17662 8550
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
8
   0.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The exact 1-sided 97.5% CI and p-value were estimated based on stratified Poisson regression with exact conditional method (including study arm and stratification factor [age group at informed consent] as strata factor and log of total number of participants for each combination of study arm and strata as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression exact conditional
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 100.00
Confidence Interval (1-Sided) 97.5%
71.62
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Occurring Post First Dose of Study Intervention
Hide Description The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring post first dose of study intervention. The severity of COVID-19 was evaluated in participants with symptoms of COVID-19. Following are the findings regarding severe of critical symptomatic COVID-19: clinical signs at rest indicative of severe systemic illness; respiratory failure; evidence of shock; significant acute renal, hepatic, or neurologic dysfunction; admission to an intensive care unit; and death.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomized participants who received at least one dose of study intervention, irrespective of their protocol adherence and continued participation in the study. Only participants who are seronegative at baseline were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 20589 10300
Measure Type: Count of Participants
Unit of Measure: Participants
5
   0.0%
16
   0.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% CI were estimated based on Poisson regression with robust variance (including study arm and age group at screening (18-65 years, ≥ 65 years) as covariates and log of the follow-up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression with robust variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 84.97
Confidence Interval (2-Sided) 95%
58.97 to 94.50
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants With COVID-19-Related Emergency Department Visits Occurring Post Second Dose of Study Intervention
Hide Description The incidence of COVID-19-related emergency department visits occurring ≥ 15 days post second dose of study intervention (key secondary endpoint).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FVS included all participants in the full analysis set who were seronegative at baseline, received 2 doses of study intervention, and who remained on-study 15 days after their second dose without having had a prior SARS-CoV-2 RT-PCR-positive confirmed COVID-19 infection.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 17662 8550
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.0%
9
   0.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% CI and p-value were estimated based on Poisson regression with robust variance (including study arm and stratification factor [age group at informed consent] as covariates, and log of the follow up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Poisson regression with robust variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 94.80
Confidence Interval (2-Sided) 95%
58.98 to 99.34
Estimation Comments [Not Specified]
12.Secondary Outcome
Title 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
Hide Description The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.
Time Frame Baseline (Day 1) and Days 15, 29, 43, and 57
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 2037 1013
Geometric Mean (95% Confidence Interval)
Unit of Measure: arbitrary units per milliliter (AU/mL)
S Antibody Titer: Baseline (Day 1) Number Analyzed 1985 participants 997 participants
53.60
(50.74 to 56.63)
54.64
(50.04 to 59.67)
S Antibody Titer: Day 15 Number Analyzed 1887 participants 946 participants
1824.54
(1699.91 to 1958.29)
53.52
(48.91 to 58.56)
S Antibody Titer: Day 29 Number Analyzed 1393 participants 683 participants
5736.56
(5343.98 to 6157.98)
54.59
(48.61 to 61.32)
S Antibody Titer: Day 43 Number Analyzed 1785 participants 881 participants
24224.11
(23044.03 to 25464.63)
58.64
(53.05 to 64.81)
S Antibody Titer: Day 57 Number Analyzed 1611 participants 772 participants
19237.18
(18211.82 to 20320.27)
60.59
(53.93 to 68.09)
RBD Antibody Titer: Baseline (Day 1) Number Analyzed 1985 participants 997 participants
134.35
(129.69 to 139.19)
139.00
(131.01 to 147.48)
RBD Antibody Titer: Day 15 Number Analyzed 1885 participants 946 participants
967.86
(899.17 to 1041.79)
138.69
(130.62 to 147.26)
RBD Antibody Titer: Day 29 Number Analyzed 1389 participants 684 participants
5132.51
(4751.09 to 5544.54)
145.08
(133.88 to 157.22)
RBD Antibody Titer: Day 43 Number Analyzed 1783 participants 881 participants
29487.39
(27987.19 to 31068.00)
146.06
(136.18 to 156.66)
RBD Antibody Titer: Day 57 Number Analyzed 1608 participants 771 participants
23360.08
(22083.19 to 24710.81)
155.15
(142.67 to 168.73)
13.Secondary Outcome
Title Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
Hide Description The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.
Time Frame Baseline (Day 1) and Days 15, 29, 43, and 57
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 2037 1013
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
S Antibody Titer: Day 15 Number Analyzed 1856 participants 935 participants
34.04
(31.63 to 36.63)
0.97
(0.94 to 1.00)
S Antibody Titer: Day 29 Number Analyzed 1369 participants 675 participants
107.83
(99.38 to 117.01)
0.92
(0.87 to 0.98)
S Antibody Titer: Day 43 Number Analyzed 1748 participants 869 participants
453.33
(423.38 to 485.40)
1.08
(1.02 to 1.14)
S Antibody Titer: Day 57 Number Analyzed 1587 participants 760 participants
364.28
(338.30 to 392.25)
1.14
(1.04 to 1.24)
RBD Antibody Titer: Day 15 Number Analyzed 1854 participants 935 participants
7.20
(6.72 to 7.72)
0.99
(0.98 to 1.01)
RBD Antibody Titer: Day 29 Number Analyzed 1365 participants 676 participants
38.83
(35.89 to 42.01)
1.01
(0.98 to 1.05)
RBD Antibody Titer: Day 43 Number Analyzed 1747 participants 869 participants
220.84
(207.94 to 234.53)
1.05
(1.01 to 1.09)
RBD Antibody Titer: Day 57 Number Analyzed 1584 participants 759 participants
174.81
(163.74 to 186.64)
1.12
(1.06 to 1.20)
14.Secondary Outcome
Title Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay
Hide Description The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to the S and RBD antigens of AZD1222 as measured by MSD serology assay is reported.
Time Frame Baseline (Day 1) and Days 15, 29, 43, and 57
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 2037 1013
Measure Type: Number
Unit of Measure: percentage of participants
S Antibody Titer: Day 15 Number Analyzed 1856 participants 935 participants
89.5 1.1
S Antibody Titer: Day 29 Number Analyzed 1369 participants 675 participants
97.1 1.8
S Antibody Titer: Day 43 Number Analyzed 1748 participants 869 participants
99.4 2.5
S Antibody Titer: Day 57 Number Analyzed 1587 participants 760 participants
99.1 3.8
RBD Antibody Titer: Day 15 Number Analyzed 1854 participants 935 participants
61.3 0.4
RBD Antibody Titer: Day 29 Number Analyzed 1365 participants 676 participants
92.2 1.2
RBD Antibody Titer: Day 43 Number Analyzed 1747 participants 869 participants
98.8 2.1
RBD Antibody Titer: Day 57 Number Analyzed 1584 participants 759 participants
98.5 3.3
15.Secondary Outcome
Title GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay
Hide Description The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.
Time Frame Baseline (Day 1) and Days 15, 29, 43, and 57
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 2037 1013
Geometric Mean (95% Confidence Interval)
Unit of Measure: AU/mL
Baseline (Day 1) Number Analyzed 1926 participants 967 participants
20.59
(20.31 to 20.88)
21.43
(20.79 to 22.09)
Day 15 Number Analyzed 1627 participants 851 participants
41.37
(38.96 to 43.93)
21.48
(20.79 to 22.20)
Day 29 Number Analyzed 1047 participants 573 participants
65.16
(59.72 to 71.09)
23.59
(22.15 to 25.13)
Day 43 Number Analyzed 1196 participants 644 participants
228.19
(212.92 to 244.57)
22.44
(21.42 to 23.51)
Day 57 Number Analyzed 743 participants 400 participants
245.56
(223.66 to 269.61)
22.79
(21.39 to 24.28)
16.Secondary Outcome
Title GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay
Hide Description The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.
Time Frame Baseline (Day 1) and Days 15, 29, 43, and 57
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 2037 1013
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
Day 15 Number Analyzed 1573 participants 825 participants
2.03
(1.91 to 2.15)
0.99
(0.98 to 1.01)
Day 29 Number Analyzed 1021 participants 561 participants
3.20
(2.94 to 3.49)
1.07
(1.02 to 1.13)
Day 43 Number Analyzed 1150 participants 620 participants
11.22
(10.48 to 12.02)
1.05
(1.00 to 1.09)
Day 57 Number Analyzed 720 participants 386 participants
12.04
(10.98 to 13.20)
1.04
(0.99 to 1.10)
17.Secondary Outcome
Title Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay
Hide Description The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (≥ 4-fold rise in titers from baseline value to 28 days post each dose) to SARS-CoV-2 neutralizing antibodies of AZD1222 as measured by pseudo-neutralization assay is reported.
Time Frame Baseline (Day 1) and Days 15, 29, 43, and 57
Hide Outcome Measure Data
Hide Analysis Population Description
The immunogenicity analysis population included all participants in the safety analysis set who had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only participants included in the substudy were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 2037 1013
Measure Type: Number
Unit of Measure: percentage of participants
Day 15 Number Analyzed 1573 participants 825 participants
24.5 0.1
Day 29 Number Analyzed 1021 participants 561 participants
40.5 2.1
Day 43 Number Analyzed 1150 participants 620 participants
84.9 2.1
Day 57 Number Analyzed 720 participants 386 participants
84.0 1.6
18.Secondary Outcome
Title Number of Participants With COVID-19 Symptomatic Illness Occurring Post First Dose of Study Intervention
Hide Description The incidence of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring post first dose of study intervention.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomized participants who received at least one dose of study intervention, irrespective of their protocol adherence and continued participation in the study. Only participants who are seronegative at baseline were analyzed.
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description:
Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29.
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Number of Participants Analyzed 20589 10300
Measure Type: Count of Participants
Unit of Measure: Participants
287
   1.4%
303
   2.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1222, Placebo
Comments The 95% CI were estimated based on Poisson regression with robust variance (including study arm and age group at screening (18-65 years, ≥ 65 years) as covariates and log of the follow-up time as an offset).
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine efficacy
Estimated Value 54.47
Confidence Interval (2-Sided) 95%
46.48 to 61.26
Estimation Comments [Not Specified]
Time Frame AEs are reported from first administration of study intervention up to clinical DCO of 05 March 2021, up to a maximum of approximately 27 weeks.
Adverse Event Reporting Description The safety analysis set included all participants who received at least one dose of study intervention. Adverse events data reported for double-blind period only. All-cause mortality data reported for overall period (double-blind period and unblinded period).
 
Arm/Group Title AZD1222 Placebo
Hide Arm/Group Description Participants were randomized to receive 2 IM doses of either 5*10^10 vp (nominal, ± 1.5*10^10 vp) AZD1222 on Days 1 and 29. Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
All-Cause Mortality
AZD1222 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   8/21587 (0.04%)      7/10792 (0.06%)    
Hide Serious Adverse Events
AZD1222 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   140/21587 (0.65%)      78/10792 (0.72%)    
Blood and lymphatic system disorders     
Anaemia  1  3/21587 (0.01%)  3 0/10792 (0.00%)  0
Blood loss anaemia  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Cardiac disorders     
Acute myocardial infarction  1  3/21587 (0.01%)  3 1/10792 (0.01%)  1
Angina pectoris  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Arrhythmia  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Atrial fibrillation  1  3/21587 (0.01%)  3 4/10792 (0.04%)  4
Atrioventricular block  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Atrioventricular block second degree  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Bradycardia  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Bundle branch block right  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Cardiac arrest  1  0/21587 (0.00%)  0 2/10792 (0.02%)  2
Cardiac failure congestive  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Chronic left ventricular failure  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Coronary artery disease  1  3/21587 (0.01%)  3 0/10792 (0.00%)  0
Myocardial infarction  1  2/21587 (0.01%)  2 2/10792 (0.02%)  2
Supraventricular tachycardia  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Congenital, familial and genetic disorders     
Haemorrhagic arteriovenous malformation  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Ear and labyrinth disorders     
Neurosensory hypoacusis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Vertigo positional  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Endocrine disorders     
Thyrotoxic crisis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Eye disorders     
Optic ischaemic neuropathy  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Retinal detachment  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Gastrointestinal disorders     
Aphthous ulcer  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Chronic gastritis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Constipation  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Diarrhoea  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Diverticulum intestinal haemorrhagic  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Duodenal ulcer haemorrhage  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Gastric ulcer haemorrhage  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Gastrointestinal haemorrhage  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Ileus  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Incarcerated inguinal hernia  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Internal hernia  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Intestinal obstruction  1  3/21587 (0.01%)  3 0/10792 (0.00%)  0
Obstructive pancreatitis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Oesophagitis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Pancreatitis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Small intestinal obstruction  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
General disorders     
Death  1  1/21587 (0.00%)  1 1/10792 (0.01%)  1
Hypothermia  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Oedema peripheral  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Hepatobiliary disorders     
Bile duct stone  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Cholecystitis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Cholecystitis acute  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Ischaemic hepatitis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Infections and infestations     
Appendicitis  1  7/21587 (0.03%)  7 3/10792 (0.03%)  3
COVID-19  1  1/21587 (0.00%)  1 5/10792 (0.05%)  5
COVID-19 pneumonia  1  3/21587 (0.01%)  3 10/10792 (0.09%)  10
Cellulitis  1  2/21587 (0.01%)  2 1/10792 (0.01%)  1
Cholecystitis infective  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Device related infection  1  2/21587 (0.01%)  2 2/10792 (0.02%)  2
Diverticulitis  1  1/21587 (0.00%)  1 1/10792 (0.01%)  1
Extradural abscess  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Gastroenteritis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Gastroenteritis viral  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Infected skin ulcer  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Peritonsillar abscess  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Pneumonia  1  7/21587 (0.03%)  7 1/10792 (0.01%)  1
Pneumonia bacterial  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Psoas abscess  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Pyelonephritis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Pyelonephritis acute  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Scrotal cellulitis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Sepsis  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Septic shock  1  3/21587 (0.01%)  3 1/10792 (0.01%)  1
Streptococcal bacteraemia  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Toxic shock syndrome staphylococcal  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Urinary tract infection  1  3/21587 (0.01%)  3 1/10792 (0.01%)  1
Viral infection  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Injury, poisoning and procedural complications     
Accident  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Ankle fracture  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Chemical peritonitis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Fall  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Femoral neck fracture  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Femur fracture  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Gun shot wound  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Hip fracture  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Ilium fracture  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Intentional overdose  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Joint dislocation  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Ligament sprain  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Median nerve injury  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Overdose  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Pneumothorax traumatic  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Rib fracture  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Road traffic accident  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Toxicity to various agents  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Traumatic intracranial haematoma  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Traumatic intracranial haemorrhage  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Traumatic liver injury  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Investigations     
Oxygen saturation decreased  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Precancerous cells present  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Metabolism and nutrition disorders     
Diabetic ketoacidosis  1  1/21587 (0.00%)  1 2/10792 (0.02%)  2
Gout  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Hypercalcaemia  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Hyponatraemia  1  0/21587 (0.00%)  0 2/10792 (0.02%)  2
Hypovolaemia  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Type 2 diabetes mellitus  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Lumbar spinal stenosis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Muscle spasms  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Osteoarthritis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Rhabdomyolysis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Spinal stenosis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Borderline mucinous tumour of ovary  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Brain neoplasm  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Breast cancer  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Choroid melanoma  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Huerthle cell carcinoma  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Intraductal proliferative breast lesion  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Invasive ductal breast carcinoma  1  3/21587 (0.01%)  3 1/10792 (0.01%)  1
Lung adenocarcinoma  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Lung neoplasm malignant  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Malignant neoplasm of pleura  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Metastatic squamous cell carcinoma  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Neuroendocrine tumour  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Papillary thyroid cancer  1  3/21587 (0.01%)  3 0/10792 (0.00%)  0
Prostate cancer  1  3/21587 (0.01%)  3 2/10792 (0.02%)  2
Prostate cancer stage III  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Transitional cell carcinoma  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Nervous system disorders     
Cerebral artery occlusion  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Chronic inflammatory demyelinating polyradiculoneuropathy  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Haemorrhagic transformation stroke  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Hypoaesthesia  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Intraventricular haemorrhage  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Ischaemic stroke  1  4/21587 (0.02%)  4 1/10792 (0.01%)  1
Lumbar radiculopathy  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Metabolic encephalopathy  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Paraesthesia  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Peripheral sensory neuropathy  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Post stroke seizure  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Sensory loss  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Syncope  1  1/21587 (0.00%)  1 1/10792 (0.01%)  1
Transient ischaemic attack  1  1/21587 (0.00%)  1 1/10792 (0.01%)  1
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Psychiatric disorders     
Anxiety  1  0/21587 (0.00%)  0 2/10792 (0.02%)  2
Major depression  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Schizoaffective disorder  1  0/21587 (0.00%)  0 1/10792 (0.01%)  2
Schizophrenia  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Suicidal ideation  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Suicide attempt  1  0/21587 (0.00%)  0 2/10792 (0.02%)  2
Renal and urinary disorders     
Acute kidney injury  1  1/21587 (0.00%)  1 3/10792 (0.03%)  3
Bladder outlet obstruction  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Nephrolithiasis  1  1/21587 (0.00%)  1 1/10792 (0.01%)  1
Reproductive system and breast disorders     
Adenomyosis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Prostatitis  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Respiratory, thoracic and mediastinal disorders     
Haemoptysis  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Haemothorax  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Pneumothorax  1  1/21587 (0.00%)  1 1/10792 (0.01%)  1
Pulmonary embolism  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Respiratory failure  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Acute respiratory distress syndrome  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Acute respiratory failure  1  1/21587 (0.00%)  1 1/10792 (0.01%)  1
Asphyxia  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Chronic obstructive pulmonary disease  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Skin and subcutaneous tissue disorders     
Petechiae  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Vascular disorders     
Aortic aneurysm rupture  1  1/21587 (0.00%)  1 0/10792 (0.00%)  0
Arterial haemorrhage  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Deep vein thrombosis  1  2/21587 (0.01%)  2 0/10792 (0.00%)  0
Hypertensive emergency  1  0/21587 (0.00%)  0 1/10792 (0.01%)  1
Hypotension  1  0/21587 (0.00%)  0 2/10792 (0.02%)  2
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
AZD1222 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6835/21587 (31.66%)      2206/10792 (20.44%)    
Gastrointestinal disorders     
Diarrhoea  1  549/21587 (2.54%)  581 235/10792 (2.18%)  250
Nausea  1  255/21587 (1.18%)  261 99/10792 (0.92%)  101
General disorders     
Chills  1  438/21587 (2.03%)  447 105/10792 (0.97%)  108
Fatigue  1  1105/21587 (5.12%)  1126 388/10792 (3.60%)  397
Injection site pain  1  1474/21587 (6.83%)  1491 219/10792 (2.03%)  222
Pain  1  1769/21587 (8.19%)  1910 249/10792 (2.31%)  265
Reactogenicity event  1  282/21587 (1.31%)  318 45/10792 (0.42%)  51
Infections and infestations     
COVID-19  1  368/21587 (1.70%)  373 352/10792 (3.26%)  352
Injury, poisoning and procedural complications     
Injection related reaction  1  328/21587 (1.52%)  375 66/10792 (0.61%)  73
Investigations     
Body temperature increased  1  742/21587 (3.44%)  772 92/10792 (0.85%)  93
Musculoskeletal and connective tissue disorders     
Arthralgia  1  252/21587 (1.17%)  268 62/10792 (0.57%)  66
Myalgia  1  444/21587 (2.06%)  450 120/10792 (1.11%)  125
Pain in extremity  1  303/21587 (1.40%)  317 76/10792 (0.70%)  77
Nervous system disorders     
Headache  1  1359/21587 (6.30%)  1427 501/10792 (4.64%)  534
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  351/21587 (1.63%)  361 217/10792 (2.01%)  231
Oropharyngeal pain  1  436/21587 (2.02%)  452 241/10792 (2.23%)  250
Rhinorrhoea  1  490/21587 (2.27%)  515 253/10792 (2.34%)  263
Cough  1  345/21587 (1.60%)  359 192/10792 (1.78%)  196
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Lead
Organization: AstraZeneca
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Publications:
CDC. (Centers for Disease Control and Prevention). Coronavirus Disease 2019 (COVID-19), Symptoms of Coronavrus. https://www.cdc.gov/coronavirus/2019-ncov/symptomstesting/ symptoms.html. Published 2020. Accessed 01 July 2020.
FDA. (Food and Drug Administration). Guidance for Industry. Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. . https://www.fda.gov/media/73679/download. Published 2007. Accessed 20 June 2020.
SPEAC. (Safety Platform for Emergency Vaccines) D2.3 Priority list of adverse events of special interest: COVID-19. Work Package: WP2 Standards and Tools. v1.1. 05 March 2020. https://media.tghn.org/articles/COVID-19_AESIs_SPEAC_V1.1_5Mar2020.pdf. Published 2020. Accessed 14 June 2020.
WHO. (World Health Organization) Coronavirus disease (COVID-19) situation report-175. 13 July 2020. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200713- covid-19-sitrep-175.pdf?sfvrsn=d6acef25_2. Published 2020. Accessed 13 July 2020.
Clinical Study Protocol - 1.0 AstraZeneca AZD1222 - D8110C00001 CONFIDENTIAL AND PROPRIETARY 92 of 92
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine. 2020;382(8):727-33. Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159(7):702-6.
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04516746    
Other Study ID Numbers: D8110C00001
First Submitted: August 17, 2020
First Posted: August 18, 2020
Results First Submitted: March 3, 2022
Results First Posted: April 1, 2022
Last Update Posted: July 21, 2022