A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza

Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 centimeter (cm). Redness and swelling were graded as mild (Grade 1): greater than (>) 2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.

Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): >2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.

Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature >=38.0 deg C and categorized as>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Vomiting graded as: G1: 1-2 times in 24 h; G2: >2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h.Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.

Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature >=38.0 deg C and categorized as>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Vomiting graded as: G1: 1-2 times in 24 h; G2: >2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h.Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.

An adverse event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.

An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.

An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.

An abnormal troponin 1 result was defined as any troponin 1 level >=0.30 nanogram per milliliter.

An abnormal troponin 1 result was defined as any troponin 1 level >=0.30 nanogram per milliliter.

An abnormal troponin 1 result was defined as any troponin 1 level >=0.30 nanogram per milliliter.

An abnormal troponin 1 result was defined as any troponin 1 level >=0.30 nanogram per milliliter.

An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.

An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.

An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.

An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.

An abnormal troponin 1 result was defined as any troponin 1 level >=0.30 nanogram per milliliter.

An abnormal troponin 1 result was defined as any troponin 1 level >=0.30 nanogram per milliliter.

An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.

An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.

Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): >2.0 cm to 5.0 cm; moderate (Grade 2): >5.0 cm to 10.0 cm; severe (Grade 3): >10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.

Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature >=38.0 deg C and categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Vomiting graded as: G1: 1-2 times in 24 h; G2: >2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h. Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.

An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.

GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. When pre-vaccination assay results were lower than the LLOQ and the post-vaccination results were greater than or equal to the LLOQ, the pre-vaccination assay results were set to LLOQ for the GMFR calculation. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. When pre-vaccination assay results were lower than the LLOQ and the post-vaccination results were greater than or equal to the LLOQ, the pre-vaccination assay results were set to LLOQ for the GMFR calculation. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Percentage of participants with HAI titer >=1:40 for each strain before vaccination and 4 weeks after vaccination is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Percentage of participants with HAI titer >=1:40 for each strain before vaccination and 4 weeks after vaccination is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.

Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).

Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).

Percentage of participants achieving HAI titers >= 1:40 for each strain at 4 weeks after last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).

Percentage of participants achieving HAI titers >= 1:40 for each strain at 4 weeks after last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).

GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original [ancestral strain: Wuhan-Hu-1; USA-WA1/2020]) neutralizing titers before study vaccination and at 4 week after vaccination were reported in this outcome measure. GMT and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.

GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original [ancestral strain: Wuhan-Hu-1; USA-WA1/2020]) neutralizing titers before study vaccination and at 4 week after vaccination was reported in this outcome measure. GMT and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.

GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original [ancestral strain: Wuhan-Hu-1; USA-WA1/2020]) neutralizing titers before study vaccination to 4 week after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rise and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.

GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original [ancestral strain: Wuhan-Hu-1; USA-WA1/2020]) neutralizing titers before study vaccination to 4 week after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rise and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.

Seroresponse was defined as achieving >= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2-Reference-Strain (ancestral strain (Wuhan-Hu-1; USA-WA1/2020) neutralizing titers at 4 weeks after study vaccination was reported in this outcome measure.

Seroresponse was defined as achieving >= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2-Reference-Strain (ancestral strain (Wuhan-Hu-1; USA-WA1/2020) neutralizing titers at 4 weeks after study vaccination was reported in this outcome measure.

GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria, A/Cambodia and B/Phuket.

GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. When pre-vaccination assay results were lower than the LLOQ and the post-vaccination results were greater than or equal to the LLOQ, the pre-vaccination assay results were set to LLOQ for the GMFR calculation. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria, A/Cambodia and B/Phuket.

Seroconversion was defined as an HAI titer <1:10 prior to vaccination and >=1:40 at the time point of interest, or an HAI titer of >=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria,

Percentage of participants with HAI titer >=1:40 for each strain before vaccination and 4 weeks after vaccination is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria, A/Cambodia and B/Phuket.

GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original [ancestral strain: Wuhan-Hu-1; USA-WA1/2020]) neutralizing titers before study vaccination and at 4 week after vaccination was reported in this outcome measure. GMT and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.

GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original [ancestral strain: Wuhan-Hu-1; USA-WA1/2020]) neutralizing titers before study vaccination to 4 week after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rise and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.

Seroresponse was defined as achieving >= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2-Reference-Strain (ancestral strain (Wuhan-Hu-1; USA-WA1/2020) neutralizing titers at 4 weeks after study vaccination was reported in this outcome measure.