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 : April 1, 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

Participant Flow

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
Arm/Group Description	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description	Participants were randomized to receive 2 intramuscular (IM) doses of either 510^10 viral particles (vp) (nominal, ± 1.510^10 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.

Baseline Characteristics

Arm/Group Title		AZD1222	Placebo	Total
Arm/Group Description		Participants were randomized to rec...	Participants were randomized to rec...	Total of all reporting groups
Arm/Group Description		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
Baseline Analysis Population Description		...
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%

Outcome Measures

1.Primary Outcome


Title	Number of Participants Achieving Binary Response
Description	A binary response, whereby a participant with negative serostatus at b...
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

Outcome Measure Data

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
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	An AE is the development of any untoward medical occurrence in a clini...
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

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least one dose of study intervention.


Arm/Group Title		AZD1222	Placebo
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
After first dose		5736 26.6%	1926 17.8%
After second dose	Number Analyzed	20773 participants	9947 participants
After second dose		5074 24.4%	1797 18.1%
After any dose	Number Analyzed	21587 participants	10792 participants
After any dose		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
Description	An SAE is an AE occurring during any study phase that fulfils one or m...
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

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least one dose of study intervention.


Arm/Group Title	AZD1222	Placebo
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
Description	Solicited AEs are local or systemic predefined events for assessment o...
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

Outcome Measure Data

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
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
Solicited local AEs: After first dose		1250 68.3%	173 18.8%
Solicited local AEs: After second dose	Number Analyzed	1829 participants	908 participants
Solicited local AEs: After second dose		977 53.4%	120 13.2%
Solicited local AEs: After any dose	Number Analyzed	1944 participants	979 participants
Solicited local AEs: After any dose		1440 74.1%	239 24.4%
Solicited systemic AEs: After first dose	Number Analyzed	1842 participants	924 participants
Solicited systemic AEs: After first dose		1191 64.7%	415 44.9%
Solicited systemic AEs: After second dose	Number Analyzed	1821 participants	905 participants
Solicited systemic AEs: After second dose		862 47.3%	314 34.7%
Solicited systemic AEs: After any dose	Number Analyzed	1947 participants	980 participants
Solicited systemic AEs: After any dose		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
Description	The incidence of the first post-intervention response (negative at bas...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title	AZD1222	Placebo
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptoma...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title	AZD1222	Placebo
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptoma...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title	AZD1222	Placebo
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptoma...
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

Outcome Measure Data

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
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptom...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title	AZD1222	Placebo
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptom...
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

Outcome Measure Data

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
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	The incidence of COVID-19-related emergency department visits occurrin...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title	AZD1222	Placebo
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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
Description	The GMT was calculated as the antilogarithm of Σ(log base 2 trans...
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

Outcome Measure Data

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
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
S Antibody Titer: Baseline (Day 1)		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
S Antibody Titer: Day 15		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
S Antibody Titer: Day 29		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
S Antibody Titer: Day 43		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
S Antibody Titer: Day 57		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
RBD Antibody Titer: Baseline (Day 1)		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
RBD Antibody Titer: Day 15		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
RBD Antibody Titer: Day 29		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
RBD Antibody Titer: Day 43		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
RBD Antibody Titer: Day 57		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
Description	The fold rise was calculated as the ratio of the post-vaccination tite...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title		AZD1222	Placebo
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
S Antibody Titer: Day 15		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
S Antibody Titer: Day 29		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
S Antibody Titer: Day 43		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
S Antibody Titer: Day 57		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
RBD Antibody Titer: Day 15		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
RBD Antibody Titer: Day 29		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
RBD Antibody Titer: Day 43		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
RBD Antibody Titer: Day 57		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
Description	The fold rise was calculated as the ratio of the post-vaccination tite...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title		AZD1222	Placebo
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
S Antibody Titer: Day 15		89.5	1.1
S Antibody Titer: Day 29	Number Analyzed	1369 participants	675 participants
S Antibody Titer: Day 29		97.1	1.8
S Antibody Titer: Day 43	Number Analyzed	1748 participants	869 participants
S Antibody Titer: Day 43		99.4	2.5
S Antibody Titer: Day 57	Number Analyzed	1587 participants	760 participants
S Antibody Titer: Day 57		99.1	3.8
RBD Antibody Titer: Day 15	Number Analyzed	1854 participants	935 participants
RBD Antibody Titer: Day 15		61.3	0.4
RBD Antibody Titer: Day 29	Number Analyzed	1365 participants	676 participants
RBD Antibody Titer: Day 29		92.2	1.2
RBD Antibody Titer: Day 43	Number Analyzed	1747 participants	869 participants
RBD Antibody Titer: Day 43		98.8	2.1
RBD Antibody Titer: Day 57	Number Analyzed	1584 participants	759 participants
RBD Antibody Titer: Day 57		98.5	3.3

15.Secondary Outcome


Title	GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay
Description	The GMT was calculated as the antilogarithm of Σ(log base 2 trans...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title		AZD1222	Placebo
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
Baseline (Day 1)		20.59 (20.31 to 20.88)	21.43 (20.79 to 22.09)
Day 15	Number Analyzed	1627 participants	851 participants
Day 15		41.37 (38.96 to 43.93)	21.48 (20.79 to 22.20)
Day 29	Number Analyzed	1047 participants	573 participants
Day 29		65.16 (59.72 to 71.09)	23.59 (22.15 to 25.13)
Day 43	Number Analyzed	1196 participants	644 participants
Day 43		228.19 (212.92 to 244.57)	22.44 (21.42 to 23.51)
Day 57	Number Analyzed	743 participants	400 participants
Day 57		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
Description	The fold rise was calculated as the ratio of the post-vaccination tite...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title		AZD1222	Placebo
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
Day 15		2.03 (1.91 to 2.15)	0.99 (0.98 to 1.01)
Day 29	Number Analyzed	1021 participants	561 participants
Day 29		3.20 (2.94 to 3.49)	1.07 (1.02 to 1.13)
Day 43	Number Analyzed	1150 participants	620 participants
Day 43		11.22 (10.48 to 12.02)	1.05 (1.00 to 1.09)
Day 57	Number Analyzed	720 participants	386 participants
Day 57		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
Description	The fold rise was calculated as the ratio of the post-vaccination tite...
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

Outcome Measure Data

Analysis Population Description


Arm/Group Title		AZD1222	Placebo
Arm/Group Description:		Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:		Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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
Day 15		24.5	0.1
Day 29	Number Analyzed	1021 participants	561 participants
Day 29		40.5	2.1
Day 43	Number Analyzed	1150 participants	620 participants
Day 43		84.9	2.1
Day 57	Number Analyzed	720 participants	386 participants
Day 57		84.0	1.6

18.Secondary Outcome


Title	Number of Participants With COVID-19 Symptomatic Illness Occurring Post First Dose of Study Intervention
Description	The incidence of SARS-CoV-2 RT-PCR-positive symptomatic illness occurr...
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

Outcome Measure Data

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
Arm/Group Description:	Participants were randomized to rec...	Participants were randomized to rec...
Arm/Group Description:	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%

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]

Adverse Events

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
Arm/Group Description	Participants were randomized to rec...		Participants were randomized to rec...
Arm/Group Description	Participants were randomized to receive 2 IM doses of either 510^10 vp (nominal, ± 1.510^10 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%)
Serious Adverse Events 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
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

Limitations and Caveats

[Not Specified]

More Information

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.

Folegatti PM, Bittaye M, Flaxman A, Lopez FR, Bellamy D, Kupke A, Mair C, Makinson R, Sheridan J, Rohde C, Halwe S, Jeong Y, Park YS, Kim JO, Song M, Boyd A, Tran N, Silman D, Poulton I, Datoo M, Marshall J, Themistocleous Y, Lawrie A, Roberts R, Berrie E, Becker S, Lambe T, Hill A, Ewer K, Gilbert S. Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial. Lancet Infect Dis. 2020 Jul;20(7):816-826. doi: 10.1016/S1473-3099(20)30160-2. Epub 2020 Apr 21. Erratum in: Lancet Infect Dis. 2020 May 12;:. Lancet Infect Dis. 2020 Jun 8;:.

Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu Rev Virol. 2016 Sep 29;3(1):237-261. Epub 2016 Aug 25. Review.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574. doi: 10.1016/S0140-6736(20)30251-8. Epub 2020 Jan 30.

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.

van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR, Avanzato VA, Bushmaker T, Flaxman A, Ulaszewska M, Feldmann F, Allen ER, Sharpe H, Schulz J, Holbrook M, Okumura A, Meade-White K, Pérez-Pérez L, Edwards NJ, Wright D, Bissett C, Gilbride C, Williamson BN, Rosenke R, Long D, Ishwarbhai A, Kailath R, Rose L, Morris S, Powers C, Lovaglio J, Hanley PW, Scott D, Saturday G, de Wit E, Gilbert SC, Munster VJ. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020 Oct;586(7830):578-582. doi: 10.1038/s41586-020-2608-y. Epub 2020 Jul 30. Erratum in: Nature. 2021 Feb;590(7844):E24.

Waldrop G, Doherty M, Vitoria M, Ford N. Stable patients and patients with advanced disease: consensus definitions to support sustained scale up of antiretroviral therapy. Trop Med Int Health. 2016 Sep;21(9):1124-30. doi: 10.1111/tmi.12746. Epub 2016 Jul 22.

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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:	April 1, 2022

To Top