A Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in Comparison With mRNA-1273 Booster Vaccine for COVID-19

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as absorbance units/millilitre (AU/mL). The GMC 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

Time frame: Day 29 (post vaccination)

Population: Per-Protocol Set for Immunogenicity-SARS-CoV-2 negative (PPSI-Neg) included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at Baseline and up to the analysis visit. Here, Number of Participants Analysed: those participants who were evaluable for this Outcome Measure.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

Time frame: Day 85 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Number of Participants Analysed signifies those participants who were evaluable for this Outcome Measure.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. The ancestral (prototype) strain was Wuhan-Hu-1. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

Time frame: Day 29 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Number of Participants Analysed signifies those participants who were evaluable for this Outcome Measure.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. The ancestral strain was Wuhan-Hu-1. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

Time frame: Day 85 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Number of Participants Analysed signifies those participants who were evaluable for this Outcome Measure.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

Time frame: Day 29 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Number of Participants Analysed signifies those participants who were evaluable for this Outcome Measure.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

Time frame: Day 85 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Number of Participants Analysed signifies those participants who were evaluable for this Outcome Measure.

An AE leading to withdrawal was defined as any AE that caused the participant to withdraw from the study, regardless of whether the decision to withdraw from the study was made by the participant or by the Investigator. A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

Time frame: Day 1 to end of study (Day 359)

Population: The Safety Set included all randomized participants who received the study vaccine. Participants were included in the study vaccine arm that they actually received.

An AESI is an AE (serious or non serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the investigator to the Sponsor was required. Such events may have required further investigation to characterize and understand them. A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

Time frame: Day 1 to end of study (Day 359)

Population: The Safety Set included all randomized participants who received the study vaccine. Participants were included in the study vaccine arm that they actually received.

An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). This would include visits to a clinic for unscheduled assessments (for example, rash assessment, abnormal laboratory follow-up, coronavirus disease 2019 \[COVID-19\]) and visits to HCPs external to the clinic (for example, urgent care, primary care physician). A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

Time frame: Day 1 to end of study (Day 359)

Population: The Safety Set included all randomized participants who received the study vaccine. Participants were included in the study vaccine arm that they actually received.

An AE was considered an SAE if, in the view of either the investigator or Sponsor, it resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization or prolongation of hospitalization in the absence of a precipitating event was not in itself an SAE), resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect, or was a medically important event. A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

Time frame: Day 1 to end of study (Day 359)

Population: The Safety Set included all randomized participants who received the study vaccine. Participants were included in the study vaccine arm that they actually received.

An AE was any untoward medical occurrence associated with the use of a drug/vaccine, whether or not considered related to the drug/vaccine. An unsolicited AE was any AE reported by the participant that was not specified as a solicited AR in the protocol or was specified as a solicited AR but starts outside the protocol-defined period for reporting solicited ARs (that is, 7 days after vaccination). A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

Time frame: Up to Day 29 (28 days post-vaccination)

Population: The Safety Set included all randomized participants who received the study vaccine. Participants were included in the study vaccine arm that they actually received.

Reactogenicity refers to the occurrence and intensity of selected signs and symptoms (ARs) occurring after vaccine injection. Participants recorded such occurrences in an electronic diary on the day of study vaccine injection and for the 7 days after the day of dosing. Solicited local ARs were injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of the injection. Solicited systemic ARs were headache, fatigue, myalgia (muscle aches all over the body), arthralgia (joint aches in several joints), nausea/vomiting, chills, and fever (oral temperature). The Investigator determined if a solicited AR was also to be recorded as an adverse event (AE). A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

Time frame: Up to Day 8 (7 days post-vaccination)

Population: The Solicited Safety Set included all randomized participants who received the study vaccine and contributed any solicited AR data within the first 7 days after study vaccine administration. Participants were included in the study vaccine arm that they actually received. Here, Overall number of Participants Analyzed signifies those participants who were evaluable for this Outcome Measure.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. The ancestral strain was Wuhan-Hu-1. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

Time frame: Day 29, Day 85, Day 179 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this Outcome Measure. Number Analyzed signifies those participants who were evaluable at specified timepoint.

Blood samples for immunogenicity assessments were collected during protocol specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.

Time frame: Day 179 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Number of Participants Analysed signifies those participants who were evaluable for this Outcome Measure.

Blood samples for immunogenicity assessments were collected during protocol specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation. Superiority at Day 29 was demonstrated if the lower bound of the 99% CI of the Geometric Mean Ratio was \>1. Superiority at Day 85 was demonstrated if the lower bound of the 96% CI of the Geometric Mean Ratio was \>1.

Time frame: Day 29 and Day 85 (post vaccination)

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this Outcome Measure. Number Analyzed signifies those participants who were evaluable at specified timepoint.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation. Other variant strains include B.1.1.7 Strain, AY.4 Strain, P.1 Strain.

Time frame: Days 29 and 85

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this Outcome Measure. Number Analyzed signifies those participants who were evaluable at specified timepoint.

Asymptomatic SARS-CoV-2 infection was defined as a positive RT-PCR test on a respiratory sample in the absence of symptoms or a positive serologic test for antinucleocapsid antibody after a negative test at time of enrollment.

Time frame: Day 14 through the end of study (Day 359)

Population: Per-Protocol Set for Efficacy included all participants with a pre-vaccination/Baseline SARS-CoV-2 negative status who received the planned dose of study vaccination and had no major protocol deviations that had an impact on key or critical data.

The primary case definition of COVID-19 (protocol-defined COVID-19) required the participant to have experienced at least 2 of the following systemic symptoms: fever, chills, myalgia, headache, sore throat, new olfactory and taste disorder(s), or the participant must have experienced at least 1 of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical or radiographical evidence of pneumonia, and must have at least 1 nasopharyngeal swab, nasal swab, or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR.

Time frame: Day 14 through the end of study (Day 359)

Population: Per-Protocol Set for Efficacy included all participants with a pre-vaccination/Baseline SARS-CoV-2 negative status who received the planned dose of study vaccination and had no major protocol deviations that had an impact on key or critical data.

The secondary case definition of COVID-19 (CDC case definition) was based on a positive RT-PCR test on a respiratory sample and at least 1 of the following systemic or respiratory symptoms: fever, chills, cough, shortness of breath, and/or difficulty breathing, fatigue, muscle and/or body aches (not related to exercise), headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhoea.

Time frame: Day 14 through the end of study (Day 359)

Population: Per-Protocol Set for Efficacy included all participants with a pre-vaccination/Baseline SARS-CoV-2 negative status who received the planned dose of study vaccination and had no major protocol deviations that had an impact on key or critical data.

Symptomatic SARS-CoV-2 infection was defined 2 ways: protocol-defined COVID-19 and Center for Disease Control (CDC) COVID-19. Protocol-defined COVID-19 required at least 2 of the following systemic symptoms: fever, chills, myalgia, headache, sore throat, new olfactory and taste disorder(s), or at least 1 of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, or clinical/radiographical evidence of pneumonia, and at least 1 positive nasopharyngeal swab, nasal swab, or saliva sample (RT-PCR). CDC-defined COVID-19 was based on a positive respiratory sample (RT-PCR) and at least 1 of the following systemic or respiratory symptoms: fever, chills, cough, shortness of breath, and/or difficulty breathing, fatigue, muscle and/or body aches, headache, new loss of taste/smell, sore throat, congestion, runny nose, nausea, vomiting, or diarrhoea.

Time frame: Day 1 through the end of study (Day 359)

Population: Per-Protocol Set for Efficacy included all participants with a pre-vaccination/Baseline SARS-CoV-2 negative status who received the planned dose of study vaccination and had no major protocol deviations that had an impact on key or critical data.

Seroresponse was defined by an increase of the GMC from pre-study vaccination (booster) below the lower limit of quantitation (LLOQ) to at least 4×LLOQ, or a 4-fold or greater rise if pre-study vaccination was ≥LLOQ. The number of participants analysed from the PPSI-Neg population include those with non-missing data at Baseline and the corresponding timepoint. 95% CI calculated using the Clopper-Pearson method.

Time frame: Days 29, 85, 179, and 359

Population: PPSI-Neg included all randomized participants who received the planned dose of study vaccine, had no major protocol deviations with an impact on critical or key study data, and had no serologic or virologic evidence of SARS-CoV-2 infection at Baseline and up to the analysis visit. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this Outcome Measure. Number Analyzed signifies those participants who were evaluable at specified timepoint.