Table 1.

Clinical Trial Designs

	Clinical trial
Trial characteristic	COVE (CoVPN3001)	AZD1222(CoVPN3002)	ENSEMBLE (CoVPN3003)	PREVENT-19 (CoVPN3004)	VAT00008(CoVPN3005)
Location of study sites	US	Chile, Peru, and US	Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, and US	Mexico and US	Colombia, Ghana, Honduras, India, Japan, Kenya, Mexico, Nepal, Nigeria, Uganda, Ukraine, and US
Key eligibility criteria^a	Aged ≥18 y and with locations or circumstances that put them at an appreciable risk of SARS-CoV-2 infection, a high risk of severe COVID-19, or both	Aged ≥18 y, with medically stable conditions, and increased risk for SARS-CoV-2 infection, including high risk for symptomatic and severe COVID-19	Aged ≥18 y, in good or stable health, and no coexisting conditions that have been associated with an increased risk of severe COVID-19	Aged ≥18 y, with substantial risk of SARS-CoV-2 exposure, and medically stable	Aged ≥18 y, not intending to receive approved COVID-19 vaccine
Key exclusion criteria^a	Known history of SARS-CoV-2 infection	History of laboratory-confirmed SARS-CoV-2 infection; any confirmed or suspected immunosuppressive or immunodeficient state	Clinically significant acute illness	Known previous laboratory-confirmed SARS-CoV-2 infection; known immunosuppression	Clinically significant medical condition and prior administration of COVID-19 vaccine
Primary dose regimen	2 Doses, 28 d apart	2 Doses, 28 d apart	1 Dose	2 Doses, 21 d apart	2 Doses, 21 d apart
Primary safety end points	Solicited local and systemic ARs through 7 d after each dose of IP; unsolicited AEs through 28 d after each dose of IP; MAAEs or AEs leading to withdrawal (entire study); SAEs (entire study)	Incidence of AEs for 28 d after each dose of IP; incidence of SAEs, MAAEs, and AESIs from 1 d post treatment through 730 d; incidence of local and systemic solicited AEs for 7 d after each dose of IP	Occurrence and relationship of SAEs (entire study), MAAEs (<6 mo post vaccination), and MAAEs leading to study discontinuation (entire study)	Incidence and severity of MAAEs and unsolicited AEs through 28 d after second injection of IP; incidence and severity of MAAEs attributed to study vaccine, SAEs, and AESIs through 2 mo, and during 12 through 24 mo or the end of study; death due to any cause	Unsolicited injection site and systemic AEs reported in the 30 min after each IP; unsolicited injection site and systemic AEs through 21 d after injection of IP; presence of MAAEs, SAEs, and AESIs throughout the study; reactogenicity subset with solicited AE 7 d after each IP
Primary efficacy end point	First occurrence of PCR-confirmed, mild, moderate, or severe to critical COVID-19, in seronegative participants	First occurrence of PCR-confirmed, mild, moderate, or severe to critical COVID-19, in seronegative participants	First occurrence of PCR-confirmed, moderate to severe to critical COVID-19, in seronegative participants	First occurrence of PCR-confirmed, mild, moderate, or severe to critical COVID-19, in seronegative participants	First occurrence of PCR-confirmed symptomatic COVID-19
Start of primary efficacy end point	14 d After second dose	14 d After second dose	14 d After vaccination	7 d After second dose	14 d After second dose
Follow-up period per participant	2 y	2 y	2 y	2 y	iy
Key secondary efficacy end points^b	Severe COVID-19 (≥14d after second dose)	Proportion of participants positive for SARS-CoV-2 infection (measured through nucleocapsid antibody seroconversion)	First occurrence of molecularly confirmed, moderate or severe to critical COVID-19, with onset 28 d post vaccination, in seronegative participants	First episode of PCR-positive COVID-19 shown by gene sequencing to represent a variant not considered as a variant of concern or interest according to the CDC's SARS-CoV-2 variant classifications and definitions¹⁴	Occurrence of SARS-CoV-2 infection and severe COVID-19 illness (≥14 d after second dose); stage 2 results are for the bivalent vaccine only.
Disease definition (all require PCR or NAAT confirmation of SARS-CoV-2 infection in addition to listed symptoms)	Cough, shortness of breath, or pneumonia (≥1); or fever (≥38 °C), chills, myalgia, headache, sore throat, anosmia, or ageusia (≥2)	1 d of Fever, dyspnea, or shortness of breath or ≥2 d of chills, cough, myalgia, fatigue, headache, vomiting, diarrhea, anosmia, ageusia, sore throat, congestion, runny nose	Respiratory symptoms or DVT (≥1); or FDA criteria for moderate COVID-19, anosmia, ageusia, red or bruised-looking feet or toes (≥2)	Fever or cough (≥1); or FDA criteria for mild COVID-19, shortness of breath, anosmia, or ageusia (≥2)	New onset of fever, shortness of breath, altered level of consciousness, myocarditis, thromboembolic event, purpura fulminans, pneumonia, chilblains (≥1) or >24 h of cough, anosmia, ageusia or ageusia (≥1) or >24 h sore throat, chills, myalgia, fatigue, malaise, headache, rhinorrhea, abdominal pain, nausea, diarrhea, or vomiting (≥2)
Severe disease definition^c	CDC criteria for severe or critical	CDC criteria for severe or critical	CDC criteria for severe or critical	CDC criteria for severe or critical	CDC criteria for severe or critical

Abbreviations: AE, adverse event; AESI, adverse event of special interest; AR, adverse reaction; CDC, Centers for Disease Control and Prevention; DVT, deep vein thrombosis; FDA, US Food and Drug Administration; IP, investigational product; MAAE, medically attended adverse event; NAAT, nucleic acid amplification test; PCR, polymerase chain reaction; SAE, serious adverse event.

A full list of inclusion and exclusion criteria can be found at the protocol links provided in the eMethods in Supplement 1.

A full list of secondary end points can be found at the protocol links provided in the eMethods in Supplement 1.

Described in text.