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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04516746
• Collaborator: Iqvia Pty Ltd (Industry)
• Enrollment: 32,459
• Locations: 84
• Arms: 2
• Anticipated Duration (Months): 29.9
• Patients Per Site: 386.4
• Patients Per Site Per Month: 12.9

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
COVID-19; SARS-CoV-2	Biological: AZD1222; Biological: Placebo	Phase 3

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 32459 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants are assigned to one of two or more groups in parallel for the duration of the study.Participants are assigned to one of two or more groups in parallel for the duration of the study.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double Blind: two or more parties are unaware of the intervention assignment.
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults, to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19
• Actual Study Start Date: Aug 28, 2020
• Actual Primary Completion Date: Mar 5, 2021
• Anticipated Study Completion Date: Feb 24, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD1222 Approximately 20,000 participants randomized to the AZD1222 arm	Biological: AZD1222; AZD1222 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2-5 surface glycoprotein.
Placebo Comparator: Placebo Approximately 10,000 participants randomized to the saline placebo arm	Biological: Placebo; Commercially available 0.9% (n/V) saline for injection.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Achieving Binary Response [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]

   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.

2. Number of Participants With Adverse Events (AEs) Occurring Post Each Dose of Study Intervention [From Day 1 up to 28 days post second dose of study intervention, approximately 57 days]

   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.

3. Number of Participants With Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE), and Adverse Event of Special Interest (AESI) Occurring Throughout the Study [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]

   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.

4. Number of Participants With Local and Systemic Solicited AEs in the Substudy Only [From Day 1 up to 7 days post each dose of study intervention, approximately 14 days]

   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.

Secondary Outcome Measures

1. Number of Participants With First Post-intervention Response for SARS-CoV-2 Nucleocapsid Antibodies Occurring Post Second Dose of Study Intervention [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]

   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).

2. 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 [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]

   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.

3. Number of Participants With First COVID-19 Symptomatic Illness Using University of Oxford-Defined Symptom Criteria Occurring Post Second Dose of Study Intervention [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]

   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.

4. Number of Participants With First Symptomatic COVID-19 Regardless of Evidence of Prior SARS-CoV-2 Infection Occurring Post Second Dose of Study Intervention [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]

   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).

5. Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Occurring Post Second Dose of Study Intervention [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]

   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).

6. Number of Participants With COVID-19 Severe or Critical Symptomatic Illness Occurring Post First Dose of Study Intervention [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]

   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.

7. Number of Participants With COVID-19-Related Emergency Department Visits Occurring Post Second Dose of Study Intervention [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]

   The incidence of COVID-19-related emergency department visits occurring ≥ 15 days post second dose of study intervention (key secondary endpoint).

8. 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 [Baseline (Day 1) and Days 15, 29, 43, and 57]

   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.

9. Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay [Baseline (Day 1) and Days 15, 29, 43, and 57]

   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.

10. Percentage of Participants With Seroresponse to the S and RBD Antigens of AZD1222 as Measured by MSD Serology Assay [Baseline (Day 1) and Days 15, 29, 43, and 57]

    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.

11. GMTs for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay [Baseline (Day 1) and Days 15, 29, 43, and 57]

    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.

12. GMFR for SARS-CoV-2 Neutralizing Antibodies as Measured by Pseudo-neutralization Assay [Baseline (Day 1) and Days 15, 29, 43, and 57]

    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.

13. Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies of AZD1222 as Measured by Pseudo-neutralization Assay [Baseline (Day 1) and Days 15, 29, 43, and 57]

    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.

14. Number of Participants With COVID-19 Symptomatic Illness Occurring Post First Dose of Study Intervention [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]

    The incidence of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring post first dose of study intervention.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Increased risk of SARS-CoV-2 infection

• Medically stable

Exclusion Criteria:

• confirmed or suspected immunosuppressive or immunodeficient state

• significant disease, disorder, or finding

• Prior or concomitant vaccine therapy for COVID-19

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85018
2	Research Site	Scottsdale	Arizona	United States	85258
3	Research Site	Little Rock	Arkansas	United States	72212
4	Research Site	Berkeley	California	United States	94705
5	Research Site	El Centro	California	United States	92243
6	Research Site	Los Angeles	California	United States	90033
7	Research Site	Los Angeles	California	United States	90095
8	Research Site	San Diego	California	United States	92103
9	Research Site	San Diego	California	United States	92134
10	Research Site	San Francisco	California	United States	94102
11	Research Site	San Francisco	California	United States	94158
12	Research Site	Torrance	California	United States	90502
13	Research Site	Denver	Colorado	United States	80204
14	Research Site	Danbury	Connecticut	United States	06810
15	Research Site	Coral Gables	Florida	United States	33134
16	Research Site	Lake Worth	Florida	United States	33462
17	Research Site	Miami Lakes	Florida	United States	33016
18	Research Site	Orlando	Florida	United States	32803
19	Research Site	Honolulu	Hawaii	United States	96814
20	Research Site	Meridian	Idaho	United States	83642
21	Research Site	Chicago	Illinois	United States	60612
22	Research Site	Indianapolis	Indiana	United States	46202
23	Research Site	Ankeny	Iowa	United States	50023
24	Research Site	Fairway	Kansas	United States	66205
25	Research Site	Kansas City	Kansas	United States	66160
26	Research Site	Wichita	Kansas	United States	67207
27	Research Site	Wichita	Kansas	United States	67214
28	Research Site	Lexington	Kentucky	United States	40509
29	Research Site	Lake Charles	Louisiana	United States	70601
30	Research Site	Monroe	Louisiana	United States	71201
31	Research Site	Baltimore	Maryland	United States	21201
32	Research Site	Baltimore	Maryland	United States	21205
33	Research Site	Bethesda	Maryland	United States	20889
34	Research Site	Boston	Massachusetts	United States	02111
35	Research Site	Boston	Massachusetts	United States	02215
36	Research Site	Ann Arbor	Michigan	United States	48109
37	Research Site	Royal Oak	Michigan	United States	48073
38	Research Site	Minneapolis	Minnesota	United States	55425
39	Research Site	Gulfport	Mississippi	United States	39503
40	Research Site	Butte	Montana	United States	59701
41	Research Site	Portsmouth	New Hampshire	United States	03801
42	Research Site	Berlin	New Jersey	United States	08009
43	Research Site	Albuquerque	New Mexico	United States	87102
44	Research Site	Bronx	New York	United States	10467
45	Research Site	Brooklyn	New York	United States	11220
46	Research Site	Mineola	New York	United States	11501
47	Research Site	New York	New York	United States	10010
48	Research Site	New York	New York	United States	10016
49	Research Site	New York	New York	United States	10032
50	Research Site	Rochester	New York	United States	14621
51	Research Site	Rochester	New York	United States	14642
52	Research Site	Valhalla	New York	United States	10595
53	Research Site	Durham	North Carolina	United States	27710
54	Research Site	Cincinnati	Ohio	United States	45229
55	Research Site	Columbus	Ohio	United States	43210
56	Research Site	Yukon	Oklahoma	United States	73099
57	Research Site	Portland	Oregon	United States	97239
58	Research Site	Pittsburgh	Pennsylvania	United States	15232
59	Research Site	Warwick	Rhode Island	United States	02886
60	Research Site	Charleston	South Carolina	United States	29425
61	Research Site	North Charleston	South Carolina	United States	29406
62	Research Site	Spartanburg	South Carolina	United States	29303
63	Research Site	Knoxville	Tennessee	United States	37920
64	Research Site	Nashville	Tennessee	United States	37203
65	Research Site	Austin	Texas	United States	78745
66	Research Site	Dallas	Texas	United States	75208
67	Research Site	Fort Sam Houston	Texas	United States	78234
68	Research Site	Houston	Texas	United States	77030
69	Research Site	McAllen	Texas	United States	78504
70	Research Site	San Antonio	Texas	United States	78236
71	Research Site	Spring	Texas	United States	77381
72	Research Site	West Jordan	Utah	United States	84088
73	Research Site	Burlington	Vermont	United States	05401
74	Research Site	Fort Belvoir	Virginia	United States	22060
75	Research Site	Richmond	Virginia	United States	23226
76	Research Site	Seattle	Washington	United States	98109
77	Research Site	South Charleston	West Virginia	United States	25309
78	Research Site	Madison	Wisconsin	United States	53792-5666
79	Research Site	Quillota		Chile	2260000
80	Research Site	Santiago		Chile	7500539
81	Research Site	Santiago		Chile	8380453
82	Research Site	Callao		Peru	0
83	Research Site	Cercado De Lima		Peru	LIMA 1
84	Research Site	Lima		Peru	Lima 27

Sponsors and Collaborators

• AstraZeneca
• Iqvia Pty Ltd

Investigators

• Principal Investigator: Ann Falsey, MD, University of Rochester
• Principal Investigator: Magda Sobieszczyk, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol - Feb 19, 2021
• Statistical Analysis Plan - Feb 28, 2021

More Information

Additional Information:

• Statistical Analysis Plan (SAP)
• D8110C00001-CSP-amendment-6_Redacted.pdf
• CSR Synopsis

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.
• Clinical Study Protocol - 1.0 AstraZeneca AZD1222 - D8110C00001 CONFIDENTIAL AND PROPRIETARY 92 of 92
• 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 V, Bushmaker T, Flaxman A, Ulaszewska M, Feldmann F, Allen ER, Sharpe H, Schulz J, Holbrook M, Okumura A, Meade-White K, Pérez-Pérez L, 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 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. bioRxiv. 2020 May 13. pii: 2020.05.13.093195. doi: 10.1101/2020.05.13.093195. Update in: Nature. 2020 Jul 30;:.
• 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.
• 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.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04516746
• Other Study ID Numbers: D8110C00001
• First Posted: Aug 18, 2020
• Last Update Posted: Jul 21, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: COVID-19 Vaccine
• Additional relevant MeSH terms: COVID-19

Study Results

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 Detail

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 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	21635	10816
Participants Who Received First Dose	21583	10796
Participants Who Received Second Dose	20769	9951
COMPLETED	0	0
NOT COMPLETED	21635	10816

Baseline Characteristics

Arm/Group Title	AZD1222	Placebo	Total
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 Participants	17662	8550	26212
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.8 (15.73)	49.9 (15.71)	49.9 (15.73)
Sex: Female, Male (Count of Participants)
Female	7740 43.8%	3721 43.5%	11461 43.7%
Male	9922 56.2%	4829 56.5%	14751 56.3%
Race/Ethnicity, Customized (Count of 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 (Count of Participants)
Multiple	421 2.4%	202 2.4%	623 2.4%
White	14011 79.3%	6755 79%	20766 79.2%
Black or African American	1401 7.9%	706 8.3%	2107 8%
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 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 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.
Measure Participants	17662	8550
Count of Participants [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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Poisson regression with robust variance
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	73.98
	Confidence Interval	(2-Sided) 95%; 65.34 to 80.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 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.
Measure Participants	21587	10792
After first dose	5736 32.5%	1926 22.5%
After second dose	5074 28.7%	1797 21%
After any dose	8771 49.7%	3201 37.4%

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 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 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.
Measure Participants	21587	10792
SAEs	140 0.8%	78 0.9%
MAAEs	1617 9.2%	815 9.5%
AESIs	525 3%	416 4.9%

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 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 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.
Measure Participants	2037	1013
Solicited local AEs: After first dose	1250 7.1%	173 2%
Solicited local AEs: After second dose	977 5.5%	120 1.4%
Solicited local AEs: After any dose	1440 8.2%	239 2.8%
Solicited systemic AEs: After first dose	1191 6.7%	415 4.9%
Solicited systemic AEs: After second dose	862 4.9%	314 3.7%
Solicited systemic AEs: After any dose	1395 7.9%	519 6.1%

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 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

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 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.
Measure Participants	17662	8550
Count of Participants [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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Poisson regression with robust variance
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	64.32
	Confidence Interval	(2-Sided) 95%; 56.05 to 71.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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

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 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.
Measure Participants	17662	8550
Count of Participants [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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Poisson regression with robust variance
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	69.65
	Confidence Interval	(2-Sided) 95%; 60.68 to 76.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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

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 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.
Measure Participants	17662	8550
Count of Participants [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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Poisson regression with robust variance
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	70.70
	Confidence Interval	(2-Sided) 95%; 61.62 to 77.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 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.
Measure Participants	18563	9031
Count of Participants [Participants]	76 0.4%	135 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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Poisson regression with robust variance
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	73.68
	Confidence Interval	(2-Sided) 95%; 65.13 to 80.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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

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 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.
Measure Participants	17662	8550
Count of Participants [Participants]	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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Poisson regression exact conditional
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	100.00
	Confidence Interval	(1-Sided) 97.5%; 71.62 to
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 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.
Measure Participants	20589	10300
Count of Participants [Participants]	5 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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Poisson regression with robust variance
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	84.97
	Confidence Interval	(2-Sided) 95%; 58.97 to 94.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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

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 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.
Measure Participants	17662	8550
Count of Participants [Participants]	1 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
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Poisson regression with robust variance
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	94.80
	Confidence Interval	(2-Sided) 95%; 58.98 to 99.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 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.
Measure Participants	2037	1013
S Antibody Titer: Baseline (Day 1)	53.60	54.64
S Antibody Titer: Day 15	1824.54	53.52
S Antibody Titer: Day 29	5736.56	54.59
S Antibody Titer: Day 43	24224.11	58.64
S Antibody Titer: Day 57	19237.18	60.59
RBD Antibody Titer: Baseline (Day 1)	134.35	139.00
RBD Antibody Titer: Day 15	967.86	138.69
RBD Antibody Titer: Day 29	5132.51	145.08
RBD Antibody Titer: Day 43	29487.39	146.06
RBD Antibody Titer: Day 57	23360.08	155.15

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 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

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 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.
Measure Participants	2037	1013
S Antibody Titer: Day 15	34.04	0.97
S Antibody Titer: Day 29	107.83	0.92
S Antibody Titer: Day 43	453.33	1.08
S Antibody Titer: Day 57	364.28	1.14
RBD Antibody Titer: Day 15	7.20	0.99
RBD Antibody Titer: Day 29	38.83	1.01
RBD Antibody Titer: Day 43	220.84	1.05
RBD Antibody Titer: Day 57	174.81	1.12

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 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

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 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.
Measure Participants	2037	1013
S Antibody Titer: Day 15	89.5 0.5%	1.1 0%
S Antibody Titer: Day 29	97.1 0.5%	1.8 0%
S Antibody Titer: Day 43	99.4 0.6%	2.5 0%
S Antibody Titer: Day 57	99.1 0.6%	3.8 0%
RBD Antibody Titer: Day 15	61.3 0.3%	0.4 0%
RBD Antibody Titer: Day 29	92.2 0.5%	1.2 0%
RBD Antibody Titer: Day 43	98.8 0.6%	2.1 0%
RBD Antibody Titer: Day 57	98.5 0.6%	3.3 0%

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 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 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.
Measure Participants	2037	1013
Baseline (Day 1)	20.59	21.43
Day 15	41.37	21.48
Day 29	65.16	23.59
Day 43	228.19	22.44
Day 57	245.56	22.79

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 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

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 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.
Measure Participants	2037	1013
Day 15	2.03	0.99
Day 29	3.20	1.07
Day 43	11.22	1.05
Day 57	12.04	1.04

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 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

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 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.
Measure Participants	2037	1013
Day 15	24.5 0.1%	0.1 0%
Day 29	40.5 0.2%	2.1 0%
Day 43	84.9 0.5%	2.1 0%
Day 57	84.0 0.5%	1.6 0%

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 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 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.
Measure Participants	20589	10300
Count of Participants [Participants]	287 1.6%	303 3.5%

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	54.47
	Confidence Interval	(2-Sided) 95%; 46.48 to 61.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 (%)	# Events	Affected / at Risk (%)	# Events
Total	8/21587 (0%)		7/10792 (0.1%)
Serious Adverse Events
	AZD1222		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/21587 (0.6%)		78/10792 (0.7%)
Blood and lymphatic system disorders
Anaemia	3/21587 (0%)	3	0/10792 (0%)	0
Blood loss anaemia	0/21587 (0%)	0	1/10792 (0%)	1
Cardiac disorders
Acute myocardial infarction	3/21587 (0%)	3	1/10792 (0%)	1
Angina pectoris	0/21587 (0%)	0	1/10792 (0%)	1
Arrhythmia	0/21587 (0%)	0	1/10792 (0%)	1
Atrial fibrillation	3/21587 (0%)	3	4/10792 (0%)	4
Atrioventricular block	0/21587 (0%)	0	1/10792 (0%)	1
Atrioventricular block second degree	1/21587 (0%)	1	0/10792 (0%)	0
Bradycardia	0/21587 (0%)	0	1/10792 (0%)	1
Bundle branch block right	1/21587 (0%)	1	0/10792 (0%)	0
Cardiac arrest	0/21587 (0%)	0	2/10792 (0%)	2
Cardiac failure congestive	1/21587 (0%)	1	0/10792 (0%)	0
Chronic left ventricular failure	1/21587 (0%)	1	0/10792 (0%)	0
Coronary artery disease	3/21587 (0%)	3	0/10792 (0%)	0
Myocardial infarction	2/21587 (0%)	2	2/10792 (0%)	2
Supraventricular tachycardia	2/21587 (0%)	2	0/10792 (0%)	0
Congenital, familial and genetic disorders
Haemorrhagic arteriovenous malformation	1/21587 (0%)	1	0/10792 (0%)	0
Ear and labyrinth disorders
Neurosensory hypoacusis	0/21587 (0%)	0	1/10792 (0%)	1
Vertigo positional	1/21587 (0%)	1	0/10792 (0%)	0
Endocrine disorders
Thyrotoxic crisis	0/21587 (0%)	0	1/10792 (0%)	1
Eye disorders
Optic ischaemic neuropathy	0/21587 (0%)	0	1/10792 (0%)	1
Retinal detachment	1/21587 (0%)	1	0/10792 (0%)	0
Gastrointestinal disorders
Aphthous ulcer	1/21587 (0%)	1	0/10792 (0%)	0
Chronic gastritis	1/21587 (0%)	1	0/10792 (0%)	0
Constipation	1/21587 (0%)	1	0/10792 (0%)	0
Diarrhoea	1/21587 (0%)	1	0/10792 (0%)	0
Diverticulum intestinal haemorrhagic	1/21587 (0%)	1	0/10792 (0%)	0
Duodenal ulcer haemorrhage	0/21587 (0%)	0	1/10792 (0%)	1
Gastric ulcer haemorrhage	1/21587 (0%)	1	0/10792 (0%)	0
Gastrointestinal haemorrhage	2/21587 (0%)	2	0/10792 (0%)	0
Ileus	1/21587 (0%)	1	0/10792 (0%)	0
Incarcerated inguinal hernia	1/21587 (0%)	1	0/10792 (0%)	0
Internal hernia	1/21587 (0%)	1	0/10792 (0%)	0
Intestinal obstruction	3/21587 (0%)	3	0/10792 (0%)	0
Obstructive pancreatitis	0/21587 (0%)	0	1/10792 (0%)	1
Oesophagitis	1/21587 (0%)	1	0/10792 (0%)	0
Pancreatitis	0/21587 (0%)	0	1/10792 (0%)	1
Small intestinal obstruction	1/21587 (0%)	1	0/10792 (0%)	0
General disorders
Death	1/21587 (0%)	1	1/10792 (0%)	1
Hypothermia	1/21587 (0%)	1	0/10792 (0%)	0
Oedema peripheral	1/21587 (0%)	1	0/10792 (0%)	0
Hepatobiliary disorders
Bile duct stone	1/21587 (0%)	1	0/10792 (0%)	0
Cholecystitis	0/21587 (0%)	0	1/10792 (0%)	1
Cholecystitis acute	2/21587 (0%)	2	0/10792 (0%)	0
Ischaemic hepatitis	0/21587 (0%)	0	1/10792 (0%)	1
Infections and infestations
Appendicitis	7/21587 (0%)	7	3/10792 (0%)	3
COVID-19	1/21587 (0%)	1	5/10792 (0%)	5
COVID-19 pneumonia	3/21587 (0%)	3	10/10792 (0.1%)	10
Cellulitis	2/21587 (0%)	2	1/10792 (0%)	1
Cholecystitis infective	1/21587 (0%)	1	0/10792 (0%)	0
Device related infection	2/21587 (0%)	2	2/10792 (0%)	2
Diverticulitis	1/21587 (0%)	1	1/10792 (0%)	1
Extradural abscess	1/21587 (0%)	1	0/10792 (0%)	0
Gastroenteritis	0/21587 (0%)	0	1/10792 (0%)	1
Gastroenteritis viral	0/21587 (0%)	0	1/10792 (0%)	1
Infected skin ulcer	1/21587 (0%)	1	0/10792 (0%)	0
Peritonsillar abscess	1/21587 (0%)	1	0/10792 (0%)	0
Pneumonia	7/21587 (0%)	7	1/10792 (0%)	1
Pneumonia bacterial	2/21587 (0%)	2	0/10792 (0%)	0
Psoas abscess	1/21587 (0%)	1	0/10792 (0%)	0
Pyelonephritis	1/21587 (0%)	1	0/10792 (0%)	0
Pyelonephritis acute	0/21587 (0%)	0	1/10792 (0%)	1
Scrotal cellulitis	0/21587 (0%)	0	1/10792 (0%)	1
Sepsis	2/21587 (0%)	2	0/10792 (0%)	0
Septic shock	3/21587 (0%)	3	1/10792 (0%)	1
Streptococcal bacteraemia	1/21587 (0%)	1	0/10792 (0%)	0
Toxic shock syndrome staphylococcal	1/21587 (0%)	1	0/10792 (0%)	0
Urinary tract infection	3/21587 (0%)	3	1/10792 (0%)	1
Viral infection	0/21587 (0%)	0	1/10792 (0%)	1
Injury, poisoning and procedural complications
Accident	1/21587 (0%)	1	0/10792 (0%)	0
Ankle fracture	1/21587 (0%)	1	0/10792 (0%)	0
Chemical peritonitis	1/21587 (0%)	1	0/10792 (0%)	0
Fall	1/21587 (0%)	1	0/10792 (0%)	0
Femoral neck fracture	1/21587 (0%)	1	0/10792 (0%)	0
Femur fracture	0/21587 (0%)	0	1/10792 (0%)	1
Gun shot wound	1/21587 (0%)	1	0/10792 (0%)	0
Hip fracture	0/21587 (0%)	0	1/10792 (0%)	1
Ilium fracture	1/21587 (0%)	1	0/10792 (0%)	0
Intentional overdose	1/21587 (0%)	1	0/10792 (0%)	0
Joint dislocation	2/21587 (0%)	2	0/10792 (0%)	0
Ligament sprain	1/21587 (0%)	1	0/10792 (0%)	0
Median nerve injury	0/21587 (0%)	0	1/10792 (0%)	1
Overdose	2/21587 (0%)	2	0/10792 (0%)	0
Pneumothorax traumatic	1/21587 (0%)	1	0/10792 (0%)	0
Rib fracture	1/21587 (0%)	1	0/10792 (0%)	0
Road traffic accident	1/21587 (0%)	1	0/10792 (0%)	0
Toxicity to various agents	1/21587 (0%)	1	0/10792 (0%)	0
Traumatic intracranial haematoma	1/21587 (0%)	1	0/10792 (0%)	0
Traumatic intracranial haemorrhage	1/21587 (0%)	1	0/10792 (0%)	0
Traumatic liver injury	1/21587 (0%)	1	0/10792 (0%)	0
Investigations
Oxygen saturation decreased	0/21587 (0%)	0	1/10792 (0%)	1
Precancerous cells present	1/21587 (0%)	1	0/10792 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/21587 (0%)	1	2/10792 (0%)	2
Gout	0/21587 (0%)	0	1/10792 (0%)	1
Hypercalcaemia	0/21587 (0%)	0	1/10792 (0%)	1
Hyponatraemia	0/21587 (0%)	0	2/10792 (0%)	2
Hypovolaemia	0/21587 (0%)	0	1/10792 (0%)	1
Type 2 diabetes mellitus	0/21587 (0%)	0	1/10792 (0%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/21587 (0%)	1	0/10792 (0%)	0
Lumbar spinal stenosis	1/21587 (0%)	1	0/10792 (0%)	0
Muscle spasms	1/21587 (0%)	1	0/10792 (0%)	0
Osteoarthritis	0/21587 (0%)	0	1/10792 (0%)	1
Rhabdomyolysis	1/21587 (0%)	1	0/10792 (0%)	0
Spinal stenosis	1/21587 (0%)	1	0/10792 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Borderline mucinous tumour of ovary	0/21587 (0%)	0	1/10792 (0%)	1
Brain neoplasm	1/21587 (0%)	1	0/10792 (0%)	0
Breast cancer	0/21587 (0%)	0	1/10792 (0%)	1
Choroid melanoma	1/21587 (0%)	1	0/10792 (0%)	0
Huerthle cell carcinoma	1/21587 (0%)	1	0/10792 (0%)	0
Intraductal proliferative breast lesion	1/21587 (0%)	1	0/10792 (0%)	0
Invasive ductal breast carcinoma	3/21587 (0%)	3	1/10792 (0%)	1
Lung adenocarcinoma	1/21587 (0%)	1	0/10792 (0%)	0
Lung neoplasm malignant	2/21587 (0%)	2	0/10792 (0%)	0
Malignant neoplasm of pleura	0/21587 (0%)	0	1/10792 (0%)	1
Metastatic squamous cell carcinoma	0/21587 (0%)	0	1/10792 (0%)	1
Neuroendocrine tumour	1/21587 (0%)	1	0/10792 (0%)	0
Papillary thyroid cancer	3/21587 (0%)	3	0/10792 (0%)	0
Prostate cancer	3/21587 (0%)	3	2/10792 (0%)	2
Prostate cancer stage III	0/21587 (0%)	0	1/10792 (0%)	1
Transitional cell carcinoma	1/21587 (0%)	1	0/10792 (0%)	0
Nervous system disorders
Cerebral artery occlusion	0/21587 (0%)	0	1/10792 (0%)	1
Chronic inflammatory demyelinating polyradiculoneuropathy	1/21587 (0%)	1	0/10792 (0%)	0
Haemorrhagic transformation stroke	0/21587 (0%)	0	1/10792 (0%)	1
Hypoaesthesia	1/21587 (0%)	1	0/10792 (0%)	0
Intraventricular haemorrhage	1/21587 (0%)	1	0/10792 (0%)	0
Ischaemic stroke	4/21587 (0%)	4	1/10792 (0%)	1
Lumbar radiculopathy	1/21587 (0%)	1	0/10792 (0%)	0
Metabolic encephalopathy	0/21587 (0%)	0	1/10792 (0%)	1
Paraesthesia	1/21587 (0%)	1	0/10792 (0%)	0
Peripheral sensory neuropathy	1/21587 (0%)	1	0/10792 (0%)	0
Post stroke seizure	1/21587 (0%)	1	0/10792 (0%)	0
Sensory loss	0/21587 (0%)	0	1/10792 (0%)	1
Syncope	1/21587 (0%)	1	1/10792 (0%)	1
Transient ischaemic attack	1/21587 (0%)	1	1/10792 (0%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	2/21587 (0%)	2	0/10792 (0%)	0
Psychiatric disorders
Anxiety	0/21587 (0%)	0	2/10792 (0%)	2
Major depression	1/21587 (0%)	1	0/10792 (0%)	0
Schizoaffective disorder	0/21587 (0%)	0	1/10792 (0%)	2
Schizophrenia	0/21587 (0%)	0	1/10792 (0%)	1
Suicidal ideation	2/21587 (0%)	2	0/10792 (0%)	0
Suicide attempt	0/21587 (0%)	0	2/10792 (0%)	2
Renal and urinary disorders
Acute kidney injury	1/21587 (0%)	1	3/10792 (0%)	3
Bladder outlet obstruction	1/21587 (0%)	1	0/10792 (0%)	0
Nephrolithiasis	1/21587 (0%)	1	1/10792 (0%)	1
Reproductive system and breast disorders
Adenomyosis	0/21587 (0%)	0	1/10792 (0%)	1
Prostatitis	0/21587 (0%)	0	1/10792 (0%)	1
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/21587 (0%)	1	0/10792 (0%)	0
Haemothorax	1/21587 (0%)	1	0/10792 (0%)	0
Pneumothorax	1/21587 (0%)	1	1/10792 (0%)	1
Pulmonary embolism	2/21587 (0%)	2	0/10792 (0%)	0
Respiratory failure	1/21587 (0%)	1	0/10792 (0%)	0
Acute respiratory distress syndrome	1/21587 (0%)	1	0/10792 (0%)	0
Acute respiratory failure	1/21587 (0%)	1	1/10792 (0%)	1
Asphyxia	0/21587 (0%)	0	1/10792 (0%)	1
Chronic obstructive pulmonary disease	2/21587 (0%)	2	0/10792 (0%)	0
Skin and subcutaneous tissue disorders
Petechiae	1/21587 (0%)	1	0/10792 (0%)	0
Vascular disorders
Aortic aneurysm rupture	1/21587 (0%)	1	0/10792 (0%)	0
Arterial haemorrhage	0/21587 (0%)	0	1/10792 (0%)	1
Deep vein thrombosis	2/21587 (0%)	2	0/10792 (0%)	0
Hypertensive emergency	0/21587 (0%)	0	1/10792 (0%)	1
Hypotension	0/21587 (0%)	0	2/10792 (0%)	2
Other (Not Including Serious) Adverse Events
	AZD1222		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6835/21587 (31.7%)		2206/10792 (20.4%)
Gastrointestinal disorders
Diarrhoea	549/21587 (2.5%)	581	235/10792 (2.2%)	250
Nausea	255/21587 (1.2%)	261	99/10792 (0.9%)	101
General disorders
Chills	438/21587 (2%)	447	105/10792 (1%)	108
Fatigue	1105/21587 (5.1%)	1126	388/10792 (3.6%)	397
Injection site pain	1474/21587 (6.8%)	1491	219/10792 (2%)	222
Pain	1769/21587 (8.2%)	1910	249/10792 (2.3%)	265
Reactogenicity event	282/21587 (1.3%)	318	45/10792 (0.4%)	51
Infections and infestations
COVID-19	368/21587 (1.7%)	373	352/10792 (3.3%)	352
Injury, poisoning and procedural complications
Injection related reaction	328/21587 (1.5%)	375	66/10792 (0.6%)	73
Investigations
Body temperature increased	742/21587 (3.4%)	772	92/10792 (0.9%)	93
Musculoskeletal and connective tissue disorders
Arthralgia	252/21587 (1.2%)	268	62/10792 (0.6%)	66
Myalgia	444/21587 (2.1%)	450	120/10792 (1.1%)	125
Pain in extremity	303/21587 (1.4%)	317	76/10792 (0.7%)	77
Nervous system disorders
Headache	1359/21587 (6.3%)	1427	501/10792 (4.6%)	534
Respiratory, thoracic and mediastinal disorders
Nasal congestion	351/21587 (1.6%)	361	217/10792 (2%)	231
Oropharyngeal pain	436/21587 (2%)	452	241/10792 (2.2%)	250
Rhinorrhoea	490/21587 (2.3%)	515	253/10792 (2.3%)	263
Cough	345/21587 (1.6%)	359	192/10792 (1.8%)	196

Limitations/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.