Trial Outcomes & Findings for A Study of S-268019 for the Prevention of COVID-19 (NCT NCT05212948)

Last Updated: 2025-11-28

Results Overview

Participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) were determined to have symptomatic COVID-19 when at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result were confirmed by the medical monitor within at least 14 days following the second vaccination. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

9902 participants

Primary outcome timeframe

From Day 43 (14 days after the second dose administration) to Day 224

Results posted on

2025-11-28

Participant Flow

Participant milestones

Participant milestones
Measure	S-268019-b Then Placebo Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period. After the Initial Vaccination Period, participants received placebo via intramuscular injection (matching S-268019-b) on Day 225 and Day 253, during the Crossover Vaccination Period.	Placebo Then S-268019-b Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period. After the Initial Vaccination Period, participants received S-268019-b via intramuscular injection on Day 225 and Day 253, during the Crossover Vaccination Period.
Crossover Vaccination Period Safety Analysis Set (SAS)	6581	3285
Initial Vaccination Period STARTED	6600	3302
Initial Vaccination Period Received At Least 1 Dose Of Study Drug	6581	3285
Initial Vaccination Period Modified Intent to Treat (mITT)	5596	2805
Initial Vaccination Period Immunogenicity Subset	64	34
Initial Vaccination Period COMPLETED	5315	2602
Initial Vaccination Period NOT COMPLETED	1285	700
Crossover Vaccination Period STARTED	5315	2602
Crossover Vaccination Period Received At Least 1 Dose Of Study Drug	5150	2502
Crossover Vaccination Period COMPLETED	5123	2503
Crossover Vaccination Period NOT COMPLETED	192	99

Reasons for withdrawal

Reasons for withdrawal
Measure	S-268019-b Then Placebo Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period. After the Initial Vaccination Period, participants received placebo via intramuscular injection (matching S-268019-b) on Day 225 and Day 253, during the Crossover Vaccination Period.	Placebo Then S-268019-b Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period. After the Initial Vaccination Period, participants received S-268019-b via intramuscular injection on Day 225 and Day 253, during the Crossover Vaccination Period.
Initial Vaccination Period Withdrawal by Subject	409	199
Initial Vaccination Period Suspected Pregnancy	1	0
Initial Vaccination Period Pregnancy	20	14
Initial Vaccination Period Physician Decision	686	401
Initial Vaccination Period Lost to Follow-up	106	42
Initial Vaccination Period Death	23	18
Initial Vaccination Period Coronavirus Disease 2019 (COVID-19)	4	3
Initial Vaccination Period Adverse Event	36	23
Crossover Vaccination Period Withdrawal by Subject	95	57
Crossover Vaccination Period Pregnancy	6	1
Crossover Vaccination Period Physician Decision	49	24
Crossover Vaccination Period Lost to Follow-up	23	8
Crossover Vaccination Period Death	10	5
Crossover Vaccination Period Adverse Event	9	4

Baseline Characteristics

Participants in the Full Analysis Set (FAS) missing baseline N-protein antibody data have been excluded.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	S-268019-b Then Placebo n=6581 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period. After the Initial Vaccination Period, participants received placebo via intramuscular injection (matching S-268019-b) on Day 225 and Day 253, during the Crossover Vaccination Period.	Placebo Then S-268019-b n=3285 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period. After the Initial Vaccination Period, participants received S-268019-b via intramuscular injection on Day 225 and Day 253, during the Crossover Vaccination Period.	Total n=9866 Participants Total of all reporting groups
Age, Customized <30 years old	1863 Participants n=6581 Participants	954 Participants n=3285 Participants	2817 Participants n=9866 Participants
Age, Customized ≥30 to <40 years old	1559 Participants n=6581 Participants	717 Participants n=3285 Participants	2276 Participants n=9866 Participants
Age, Customized ≥40 to <50 years old	1194 Participants n=6581 Participants	616 Participants n=3285 Participants	1810 Participants n=9866 Participants
Age, Customized ≥50 to <60 years old	1017 Participants n=6581 Participants	521 Participants n=3285 Participants	1538 Participants n=9866 Participants
Age, Customized ≥60 to <65 years old	418 Participants n=6581 Participants	215 Participants n=3285 Participants	633 Participants n=9866 Participants
Age, Customized ≥65 years old	530 Participants n=6581 Participants	262 Participants n=3285 Participants	792 Participants n=9866 Participants
Sex: Female, Male Female	2151 Participants n=6581 Participants	1131 Participants n=3285 Participants	3282 Participants n=9866 Participants
Sex: Female, Male Male	4430 Participants n=6581 Participants	2154 Participants n=3285 Participants	6584 Participants n=9866 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=6581 Participants	5 Participants n=3285 Participants	23 Participants n=9866 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6552 Participants n=6581 Participants	3269 Participants n=3285 Participants	9821 Participants n=9866 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=6581 Participants	11 Participants n=3285 Participants	22 Participants n=9866 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=6581 Participants	0 Participants n=3285 Participants	2 Participants n=9866 Participants
Race (NIH/OMB) Asian	6569 Participants n=6581 Participants	3275 Participants n=3285 Participants	9844 Participants n=9866 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6581 Participants	0 Participants n=3285 Participants	0 Participants n=9866 Participants
Race (NIH/OMB) Black or African American	0 Participants n=6581 Participants	1 Participants n=3285 Participants	1 Participants n=9866 Participants
Race (NIH/OMB) White	0 Participants n=6581 Participants	0 Participants n=3285 Participants	0 Participants n=9866 Participants
Race (NIH/OMB) More than one race	0 Participants n=6581 Participants	0 Participants n=3285 Participants	0 Participants n=9866 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=6581 Participants	9 Participants n=3285 Participants	19 Participants n=9866 Participants
anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) N-protein Antibody Test Positive	816 Participants n=6535 Participants • Participants in the Full Analysis Set (FAS) missing baseline N-protein antibody data have been excluded.	409 Participants n=3269 Participants • Participants in the Full Analysis Set (FAS) missing baseline N-protein antibody data have been excluded.	1225 Participants n=9804 Participants • Participants in the Full Analysis Set (FAS) missing baseline N-protein antibody data have been excluded.
anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) N-protein Antibody Test Negative	5719 Participants n=6535 Participants • Participants in the Full Analysis Set (FAS) missing baseline N-protein antibody data have been excluded.	2860 Participants n=3269 Participants • Participants in the Full Analysis Set (FAS) missing baseline N-protein antibody data have been excluded.	8579 Participants n=9804 Participants • Participants in the Full Analysis Set (FAS) missing baseline N-protein antibody data have been excluded.

PRIMARY outcome

Timeframe: From Day 43 (14 days after the second dose administration) to Day 224

Population: Modified Intent to Treat (mITT) population: all participants who received at least 1 dose of the study intervention in the Initial Vaccination Period, excluding participants who had evidence of past or present SARS-CoV-2 infection at baseline. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure. Only data collected during the Initial Vaccination Period reported for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=2595 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=5156 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 Reverse Transcription Polymerase Chain Reaction (RT-PCR)-Positive Symptomatic COVID-19 With Onset at Least 14 Days Following Second Vaccination During the Initial Vaccination Period	239 Participants	323 Participants

SECONDARY outcome

Timeframe: From Day 43 (14 days after the second dose administration) to Day 224

Population: Modified Intent to Treat (mITT): participants who received at least 1 dose of study drug, excluding participants who had evidence of past or present SARS-CoV-2 infection at baseline. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure. Only data collected during the Initial Vaccination Period reported for this outcome measure.

For participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) who were confirmed to have symptomatic COVID-19 within at least 14 days following the second vaccination, the investigator evaluated if the maximum intensity during the course of the disease met protocol-specified criteria for severe COVID-19.

Outcome measures

Outcome measures
Measure	Placebo n=2617 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=5181 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period With Onset at Least 14 Days Following Second Vaccination	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 224

Participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) were determined to have symptomatic COVID-19 when at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result were confirmed by the medical monitor. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.

Outcome measures

Outcome measures
Measure	Placebo n=2805 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=5595 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period	313 Participants	457 Participants

SECONDARY outcome

Timeframe: Up to Day 224

Population: Modified Intent to Treat (mITT): participants who received at least 1 dose of study drug, excluding participants who had evidence of past or present SARS-CoV-2 infection at baseline. Only data collected during the Initial Vaccination Period reported for this outcome measure.

For participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline) who were confirmed to have symptomatic COVID-19, the investigator evaluated if the maximum intensity during the course of the disease met the protocol-specified criteria for severe COVID-19.

Outcome measures

Outcome measures
Measure	Placebo n=2805 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=5596 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 43 (14 days after the second dose administration) to Day 224

Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of the study intervention during the Initial Vaccination Period. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure. Only data collected during the Initial Vaccination Period reported for this outcome measure.

A participant was determined to have symptomatic COVID-19 when at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result were confirmed by the medical monitor within at least 14 days following the second vaccination. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.

Outcome measures

Outcome measures
Measure	Placebo n=3012 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=6023 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period Regardless of Serostatus or PCR Status at Baseline With Onset at Least 14 Days Following Second Vaccination	242 Participants	331 Participants

SECONDARY outcome

Timeframe: From Day 43 (14 days after the second dose administration) to Day 224

For participants confirmed to have symptomatic COVID-19 within at least 14 days following the second vaccination, the investigator evaluated if the maximum intensity during the course of the disease met the protocol-specified criteria for severe COVID-19.

Outcome measures

Outcome measures
Measure	Placebo n=3034 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=6049 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period With Onset at Least 14 Days Following Second Vaccination Regardless of Serostatus or PCR Status at Baseline	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 224

A participant was determined to have symptomatic COVID-19 when the participant had at least 1 protocol-specified COVID-19-related symptom and a positive RT-PCR test result confirmed by the medical monitor. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints.

Outcome measures

Outcome measures
Measure	Placebo n=3285 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=6579 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period Regardless of Serostatus or PCR Status at Baseline	324 Participants	479 Participants

SECONDARY outcome

Timeframe: Up to Day 224

Population: Full Analysis Set (FAS): all randomized participants who received at least 1 dose of the study intervention during the Initial Vaccination Period. Only data collected during the Initial Vaccination Period reported for this outcome measure.

For participants confirmed to have symptomatic COVID-19, the investigator evaluated if the maximum intensity during the course of the disease met the protocol-specified criteria for severe COVID-19.

Outcome measures

Outcome measures
Measure	Placebo n=3285 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=6581 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period Regardless of Serostatus or PCR Status at Baseline	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 43 (14 days after the second dose administration) to Day 224

For participants without evidence of infection before vaccination (that is, seronegative and PCR-negative at baseline), asymptomatic SARS-CoV-2 infection was defined as having a positive result of anti-SARS-CoV-2 N-protein antibody test beginning 14 days following the second vaccination and not meeting the protocol-specified criteria of symptomatic COVID-19. Antibodies to SARS-CoV-2 N-protein were used to determine both natural infection and the incidence of asymptomatic infection acquired during the initial vaccination period of the study.

Outcome measures

Outcome measures
Measure	Placebo n=2595 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=5156 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Number of Participants With First Occurrence of Asymptomatic SARS-CoV-2 Infection in the Initial Vaccination Period	1345 Participants	2543 Participants

SECONDARY outcome

Timeframe: Up to Day 224

Population: Safety Analysis Set (SAS): all randomized participants who received at least 1 dose of study intervention. Only data collected during the Initial Vaccination Period reported for this outcome measure.

An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs were defined as the AEs that occurred within the first 7 days after each vaccination and were classified as one of the following: fever, nausea/vomiting, diarrhea, headache, fatigue, and myalgia. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Outcome measures

Outcome measures
Measure	Placebo n=3285 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=6581 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Percentage of Participants Experiencing Solicited Systemic Adverse Events	23.4 Percentage of Participants Interval 22.0 to 24.9	32.7 Percentage of Participants Interval 31.5 to 33.8

SECONDARY outcome

Timeframe: Up to Day 224

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited local AEs were defined as the AEs that occurred within the first 7 days after each vaccination and were classified as one of the following: pain, erythema/redness, induration, and swelling. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Outcome measures

Outcome measures
Measure	Placebo n=3285 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=6581 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Percentage of Participants Experiencing Solicited Local Adverse Events	14.6 Percentage of Participants Interval 13.4 to 15.8	37.7 Percentage of Participants Interval 36.5 to 38.9

SECONDARY outcome

Timeframe: Day 57

Population: Immunogenicity Subset: participants who received at least 1 dose of study drug, excluding participants with evidence of past or present SARS-CoV-2 infection at baseline, and had a valid immunogenicity test result prior to the first vaccination dose and at least 1 valid result after the first vaccination dose. 'Overall Number of Participants Analyzed' are participants evaluable for this outcome measure. Only data collected during the Initial Vaccination Period reported for this outcome measure.

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 was measured by a live virus neutralization assay. The GMT was calculated by taking the back transformation of the arithmetic mean of log-transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the log-transformed values, then back transformed to the original scale.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=58 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Antibody	2.69 Titer Interval 2.31 to 3.14	34.66 Titer Interval 27.04 to 44.41

SECONDARY outcome

Timeframe: Day 57

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 was measured by a live virus neutralization assay. The GMFR was calculated by taking the back transformation of the arithmetic mean of the change from baseline in log-transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the change from baseline in the log-transformed values, then back transformed to the original scale.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=58 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody	1.08 Fold Rise Interval 0.92 to 1.25	13.86 Fold Rise Interval 10.82 to 17.76

SECONDARY outcome

Timeframe: Day 57

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 was measured by a live virus neutralization assay. Seroconversion was defined as a 4-times or higher from baseline in SARS-CoV-2 neutralizing antibody titer, where titer values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Seroconversion rate was defined as the percentage of participants that underwent seroconversion. The 95% confidence interval was calculated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=58 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Seroconversion Rate of SARS-CoV-2 Neutralizing Antibody	3.6 Percentage of Participants Interval 0.1 to 18.3	93.1 Percentage of Participants Interval 83.3 to 98.1

SECONDARY outcome

Timeframe: Day 57

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody level against SARS-CoV-2 (anti-spike protein IgG antibody) was measured by a chemiluminescence immunoassay. The GMT was calculated by taking the back transformation of the arithmetic mean of log- transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the log-transformed values, then back transformed to the original scale.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=58 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
GMT of Anti-SARS-CoV-2 S-protein Immunoglobulin G (IgG) Antibody	6.39 Titer Interval 3.1 to 13.19	25209.25 Titer Interval 17163.57 to 37026.44

SECONDARY outcome

Timeframe: Day 57

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The anti-spike protein IgG antibody was measured by a chemiluminescence immunoassay. The GMFR was calculated by taking the back transformation of the arithmetic mean of the change from baseline in log-transformed titers. The 95% confidence interval was calculated based on the Student's t distribution of the change from baseline in the log-transformed values, then back transformed to the original scale.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=57 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
GMFR of Anti-SARS-CoV-2 S-protein IgG Antibody	1.46 Fold Rise Interval 0.75 to 2.85	6710.95 Fold Rise Interval 4556.29 to 9884.54

SECONDARY outcome

Timeframe: Day 57

Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The anti-spike protein IgG antibody was measured by a chemiluminescence immunoassay. Seroconversion was defined as a 4-times or higher from baseline in anti-spike protein IgG antibody titer, where titer values reported as below the LLOQ are replaced by 0.5\*LLOQ and titer values reported as above the upper limit of quantification (ULOQ) are imputed at the ULOQ value. Seroconversion rate was defined as the percentage of participants that underwent seroconversion. The 95% confidence interval was calculated using the Clopper-Pearson method.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period.	S-268019-b n=57 Participants Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period.
Seroconversion Rate of Anti-SARS-CoV-2 S-protein IgG Antibody	7.1 Percentage of Participants Interval 0.9 to 23.5	98.2 Percentage of Participants Interval 90.6 to 100.0

Adverse Events

S-268019-b

Serious events: 154 serious events

Other events: 3647 other events

Deaths: 29 deaths

Placebo

Serious events: 136 serious events

Other events: 1548 other events

Deaths: 29 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	S-268019-b n=9083 participants at risk Participants received a dose of S-268019-b via intramuscular injection on Day 1 and Day 29 during the Initial Vaccination Period and then on Day 225 and Day 253 during the Crossover Vaccination Period.	Placebo n=8435 participants at risk Participants received a dose of placebo via intramuscular injection (matching S-268019-b) on Day 1 and Day 29 during the Initial Vaccination Period and then on Day 225 and Day 253 during the Crossover Vaccination Period.
Nervous system disorders Headache	13.6% 1235/9083 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.	5.3% 446/8435 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.
Musculoskeletal and connective tissue disorders Myalgia	11.3% 1029/9083 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.	3.0% 255/8435 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.
General disorders Pain	18.6% 1689/9083 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.	3.4% 290/8435 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.
General disorders Fatigue	15.5% 1405/9083 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.	5.5% 468/8435 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.
General disorders Injection site pain	10.2% 923/9083 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.	2.6% 219/8435 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.
General disorders Pyrexia	7.4% 676/9083 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.	2.2% 185/8435 • Day 1 (Baseline) through Day 435 All reported safety data based upon Safety Analysis Set: all randomized participants who received at least 1 dose of study intervention. Safety data presented per pre-specified analysis plan. All deaths regardless of causality or whether they were reported as a reason for study discontinuation or as a serious adverse event are reported in the All-Cause Mortality section. Only deaths indicated as leading to study discontinuation are reported in the Participant Flow section.

Additional Information

Shionogi Clinical Trials Administrator Clinical Support Help Line

Shionogi

Phone: 1-800-849-9707

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can embargo results from a PIs center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 45 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Publication restrictions are in place

Restriction type: OTHER