Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Japanese Adults

GMFR was defined as the result after vaccination divided by the result before vaccination. GMFR and the corresponding 2-sided 95% CIs was calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t distribution). GMFR of SARS-CoV-2 NT50 was reported in this outcome measure.

Time frame: Before vaccination up to 1 month after Dose 2

Population: EIP: all randomized participants who received 2 doses of the assigned vaccine, with Dose 2 received within the predefined window (within 19-42 days after Dose 1), had at least 1 valid and determinate immunogenicity result from the blood collection within an appropriate window after Dose 2 (within 28-42 days after Dose 2) and had no other major protocol deviations as determined by clinician.

GMT of SARS-CoV-2 neutralizing titer was calculated by exponentiating the mean logarithm of the titers and the corresponding 95% confidence interval (CI) was based on the Student's t distribution. GMT of SARS-CoV-2 neutralization titer 50% (NT50) was reported in this outcome measure.

Time frame: 1 month after Dose 2

Population: Evaluable immunogenicity population (EIP): all randomized participants who received 2 doses of the assigned vaccine, with Dose 2 received within the predefined window (within 19-42 days after Dose 1), had at least 1 valid and determinate immunogenicity result from the blood collection within an appropriate window after Dose 2 (within 28-42 days after Dose 2) and had no other major protocol deviations as determined by clinician.

The pre-defined criteria for laboratory parameters included: hemoglobin (HGB), hematocrit, erythrocytes(ery.) less than (\<)0.8\* lower limit of normal (LLN); ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration \<0.9\*LLN and \>1.1\*upper limit of normal (ULN); platelets \<0.5\*LLN and \>1.75\*ULN; leukocytes \<0.6\*LLN and \>1.5\*ULN; lymphocytes, neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; bilirubin \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase \>3.0\*ULN; urea nitrogen, creatinine \>1.3\*ULN. Percentage of participants with abnormal hematology and chemistry laboratory values by age categories 20 to 64 years and 65 to 85 years were reported in this outcome measure. Categories with at least 1 non-zero data values were reported.

Time frame: Within 1 day after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants with at least one result for the laboratory test after study vaccination.

The pre-defined criteria for laboratory parameters included: HGB, hematocrit, ery. \<0.8\* LLN; ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration \<0.9\*LLN and \>1.1\*ULN; platelets \<0.5\*LLN and \>1.75\*ULN; leukocytes \<0.6\*LLN and \>1.5\*ULN; lymphocytes, neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; bilirubin \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase \>3.0\*ULN; urea nitrogen, creatinine \>1.3\*ULN. Percentage of participants with abnormal hematology and chemistry laboratory values by age categories 20 to 64 years and 65 to 85 years were reported in this outcome measure. Categories with at least 1 non-zero data values were reported.

Time frame: Within 7 days after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants with at least one result for the laboratory test after study vaccination.

The pre-defined criteria for laboratory parameters included: HGB, hematocrit, ery. \<0.8\* LLN; ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration \<0.9\*LLN and \>1.1\*ULN; platelets \<0.5\*LLN and \>1.75\*ULN; leukocytes \<0.6\*LLN and \>1.5\*ULN; lymphocytes, neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; bilirubin \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase \>3.0\*ULN; urea nitrogen, creatinine \>1.3\*ULN. Categories with at least 1 non-zero data value were reported (only 65-85 years: Lymphocytes category was reported).

Time frame: Within 7 days after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants with at least one result for the laboratory test after study vaccination.

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants with AEs and the associated 95% confidence interval (CI) based on the Clopper and Pearson method was presented. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: Dose 1 up to 1 month after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention.

Local reactions included pain at injection site, redness and swelling and were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: greater than (\>) 2.0 to 5.0 cm, moderate: \>5.0 to 10.0 cm, severe: \>10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Events were classified as Grade 4 based on study investigator's judgement. Maximum severity was the highest grade within 7 days after vaccination among severity grades where the answers were neither no nor missing for at least 1 day.

Time frame: Within 7 days after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention.

Local reactions included pain at injection site, redness and swelling and were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: \> 2.0 to 5.0 cm, moderate: \>5.0 to 10.0 cm, severe: \>10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Events were classified as Grade 4 based on study investigator's judgement. Maximum severity was the highest grade within 7 days after vaccination among severity grades where the answers were neither no nor missing for at least 1 day.

Time frame: Within 7 days after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

SAE was defined as any untoward medical occurrence that, at any dose, resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or considered an important medical event. Percentage of participants with SAEs and the associated 95% CI based on the Clopper and Pearson method was presented.

Time frame: Dose 1 up to 12 months after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention.

Hematology parameters: hemoglobin, eosinophils, lymphocytes decrease, neutrophil decrease, platelets decrease, white blood cell (WBC) decrease, WBC increase. Chemistry parameters: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, bilirubin increased, creatinine increased, blood urea nitrogen. Laboratory abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology and chemistry laboratory values by age categories (20 to 64 years and 65 to 85 years) were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 day after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.

Time frame: From baseline (observation prior to Dose 1) up to 1 day after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants with at least 1 result for the laboratory test for both baseline and postvaccination visits.

Hematology parameters included: hemoglobin, eosinophils, lymphocytes decrease, neutrophil decrease, platelets decrease, WBC decrease, WBC increase. Chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, bilirubin increased, creatinine increased, urea nitrogen. Laboratory abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology and chemistry laboratory values by age categories (20 to 64 years and 65 to 85 years) were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in grade from baseline to 7 days after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.

Time frame: From baseline (observation prior to Dose 1) up to 7 days after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants with at least 1 result for the laboratory test for both baseline and postvaccination visits.

Hematology parameters included: hemoglobin, eosinophils, lymphocytes decrease, neutrophil decrease, platelets decrease, WBC decrease, WBC increase. Chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, bilirubin increased, creatinine increased, urea nitrogen. Laboratory abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3= severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology and chemistry laboratory values by age categories (20 to 64 years and 65 to 85 years) were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in grade from before dose 2 to 7 days after dose 2 were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.

Time frame: Before Dose 2 up to 7 days after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants with at least 1 result for the laboratory test for both baseline and postvaccination visits.

Systemic events were recorded by participants in e-diary. Fever was categorized as greater than or equal to (\>=)37.5 to 38.4 degrees(deg) Celsius(C), \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: \>2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. Events were classified as Grade 4 potentially life threatening (emergency room visit or hospitalization) based on study investigator's judgement. Maximum severity=highest grade within 7 days after vaccination among severity grades where the answers were neither no nor missing for at least 1 day.

Time frame: Within 7 days after Dose 1

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention.

Systemic events were recorded by participants in an e-diary. Fever was categorized as \>= 37.5 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24h, moderate: \>2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. Events were classified as Grade 4 potentially life threatening (emergency room visit or hospitalization) based on study investigator's judgement. Maximum severity=highest grade within 7 days after vaccination among severity grades where the answers were neither no nor missing for at least 1 day.

Time frame: Within 7 days after Dose 2

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.

GMFR was defined as the result after vaccination divided by the result before vaccination. GMFRs and the corresponding 2-sided 95% CIs were planned to be calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t distribution).

Time frame: Before vaccination up to 21 days after Dose 1; 7 and 14 days after Dose 2 and 1, 6 and 12 months after Dose 2

Population: Data was not analyzed as there were no participants with or without confirmed COVID-19 before Dose 2 prior to unblinding.

GMFR was defined as the result after vaccination divided by the result before vaccination. GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t distribution). GMFRs of SARS-CoV-2 NT50 and NT90 were reported in this outcome measure.

Time frame: NT50: Before vaccination up to 21 days after Dose 1; 7 and 14 days and 6 and 12 months after Dose 2; NT90: Before vaccination up to 21 days after Dose 1; 7 and 14 days after Dose 2

Population: EIP: all randomized participants who received 2 doses of the assigned vaccine, with Dose 2 received within the predefined window (within 19-42 days after Dose 1), had at least 1 valid and determinate immunogenicity result from the blood collection within an appropriate window after Dose 2 (within 28-42 days after Dose 2) and had no other major protocol deviations as determined by clinician. Number Analyzed signifies participants evaluable for this outcome measure at specified time points.

GMTs of SARS-CoV-2 neutralizing titers was planned to be calculated by exponentiating the mean logarithm of the titers and the corresponding 95% CI was based on the Student's t distribution.

Time frame: Baseline (observation prior to Dose 1), 21 days after Dose 1; 7 and 14 days and 1, 6 and 12 months after Dose 2

Population: Data was not analyzed as there were no participants with or without confirmed COVID-19 before Dose 2 prior to unblinding.

GMTs of SARS-CoV-2 neutralizing titers were calculated by exponentiating the mean logarithm of the titers and the corresponding 95% CI was based on the Student's t distribution. GMTs of SARS-CoV-2 NT50 and neutralization titer 90% (NT90) were reported in this outcome measure.

Time frame: NT50: Baseline (observation prior to Dose 1), 21 days after Dose 1; 7 and 14 days and 6 and 12 months after Dose 2; NT90: Baseline (observation prior to Dose 1), 21 days after Dose 1; 7 and 14 days after Dose 2

Population: EIP: all randomized participants who received 2 doses of the assigned vaccine, with Dose 2 received within the predefined window (within 19-42 days after Dose 1), had at least 1 valid and determinate immunogenicity result from the blood collection within an appropriate window after Dose 2 (within 28-42 days after Dose 2) and had no other major protocol deviations as determined by clinician. Number Analyzed signifies participants evaluable for this outcome measure at specified time points.