SARS-CoV-2
Conditions
Brief summary
The main purpose of this study is to assess the efficacy of S-268019-b for the prevention of COVID-19 in the initial vaccination period prior to crossover in participants without evidence of infection before vaccination as compared to placebo.
Detailed description
Eligible participants will be randomized to receive either S-268019-b or placebo first and then will be crossed over to receive the opposite intervention. The study will consist of two treatment periods, an initial vaccination period (Day 1 to Day 224), and a crossover vaccination period (Day 225 to Day 435).
Interventions
DRUGS-268019-b
Solution for IM injection
DRUGPlacebo
Saline solution for IM injection
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Agree not to participate in any other SARS-CoV-2 prevention trial during the study follow-up. * Capable of using Diary without difficulties (if applicable, with assistance by caregiver).
Exclusion criteria
* Current or history of a laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19. * Unstable current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disease that, in the opinion of the investigator or subinvestigator, would constitute a safety concern or confound data interpretation. * Immunosuppression (immunodeficiency, acquired immunodeficiency syndrome \[AIDS\], use of systemic steroids, use of immunosuppressants within the past 6 months prior to the first dose of study intervention, treatment for malignant tumors, other immunosuppressive therapy). * Previous vaccination against SARS-CoV-2. * Any inactivated vaccine received within 14 days prior to the first dose of study intervention. * Any live vaccine received within 28 days prior to the first dose of study intervention. * Immunoglobulin preparations, blood products, or a blood transfusion within 3 months prior to the first dose of study intervention. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From Day 43 (14 days after the second dose administration) 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 within at least 14 days following the second vaccination. RT-PCR testing was based upon nasopharyngeal swab sampling at protocol-specified timepoints. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period | 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. |
| Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period | Up to Day 224 | 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. |
| 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 | From Day 43 (14 days after the second dose administration) to Day 224 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | Up to Day 224 | 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. |
| Number of Participants With First Occurrence of Asymptomatic SARS-CoV-2 Infection in the Initial Vaccination Period | 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. |
| 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 | 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) 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. |
| Percentage of Participants Experiencing Solicited Local Adverse Events | 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. |
| Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Antibody | 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 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. |
| Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody | 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. |
| Seroconversion Rate of SARS-CoV-2 Neutralizing Antibody | 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. |
| GMT of Anti-SARS-CoV-2 S-protein Immunoglobulin G (IgG) Antibody | 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. |
| GMFR of Anti-SARS-CoV-2 S-protein IgG Antibody | 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. |
| Seroconversion Rate of Anti-SARS-CoV-2 S-protein IgG Antibody | 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. |
| Percentage of Participants Experiencing Solicited Systemic Adverse Events | Up to Day 224 | 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. |
Countries
Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6,581 |
| 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. | 3,285 |
| Total | 9,866 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Crossover Vaccination Period | Adverse Event | 9 | 4 |
| Crossover Vaccination Period | Death | 10 | 5 |
| Crossover Vaccination Period | Lost to Follow-up | 23 | 8 |
| Crossover Vaccination Period | Physician Decision | 49 | 24 |
| Crossover Vaccination Period | Pregnancy | 6 | 1 |
| Crossover Vaccination Period | Withdrawal by Subject | 95 | 57 |
| Initial Vaccination Period | Adverse Event | 36 | 23 |
| Initial Vaccination Period | Coronavirus Disease 2019 (COVID-19) | 4 | 3 |
| Initial Vaccination Period | Death | 23 | 18 |
| Initial Vaccination Period | Lost to Follow-up | 106 | 42 |
| Initial Vaccination Period | Physician Decision | 686 | 401 |
| Initial Vaccination Period | Pregnancy | 20 | 14 |
| Initial Vaccination Period | Suspected Pregnancy | 1 | 0 |
| Initial Vaccination Period | Withdrawal by Subject | 409 | 199 |
Baseline characteristics
| Characteristic | S-268019-b Then Placebo | Placebo Then S-268019-b | Total |
|---|---|---|---|
| Age, Customized ≥30 to <40 years old | 1559 Participants | 717 Participants | 2276 Participants |
| Age, Customized <30 years old | 1863 Participants | 954 Participants | 2817 Participants |
| Age, Customized ≥40 to <50 years old | 1194 Participants | 616 Participants | 1810 Participants |
| Age, Customized ≥50 to <60 years old | 1017 Participants | 521 Participants | 1538 Participants |
| Age, Customized ≥60 to <65 years old | 418 Participants | 215 Participants | 633 Participants |
| Age, Customized ≥65 years old | 530 Participants | 262 Participants | 792 Participants |
| anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) N-protein Antibody Test Negative | 5719 Participants | 2860 Participants | 8579 Participants |
| anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) N-protein Antibody Test Positive | 816 Participants | 409 Participants | 1225 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 5 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6552 Participants | 3269 Participants | 9821 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 11 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 6569 Participants | 3275 Participants | 9844 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 9 Participants | 19 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2151 Participants | 1131 Participants | 3282 Participants |
| Sex: Female, Male Male | 4430 Participants | 2154 Participants | 6584 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 29 / 9,083 | 29 / 8,435 |
| other Total, other adverse events | 3,647 / 9,083 | 1,548 / 8,435 |
| serious Total, serious adverse events | 154 / 9,083 | 136 / 8,435 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | 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 | 323 Participants |
| Placebo | 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 |
Comparison: Vaccine efficacy was calculated with its 95% confidence interval and defined as 1 minus the relative risk (S-268019-b versus placebo), which included the intervention group, baseline age (continuous) as factors as well as the log of the follow-up time as an offset.p-value: 0.240995% CI: [21.9, 44.6]Poisson Regression Model
Secondary
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S-268019-b | Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody | 13.86 Fold Rise |
| Placebo | Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody | 1.08 Fold Rise |
Secondary
Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Antibody
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S-268019-b | Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Antibody | 34.66 Titer |
| Placebo | Geometric Mean Titer (GMT) of SARS-CoV-2 Neutralizing Antibody | 2.69 Titer |
Secondary
GMFR of Anti-SARS-CoV-2 S-protein IgG Antibody
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S-268019-b | GMFR of Anti-SARS-CoV-2 S-protein IgG Antibody | 6710.95 Fold Rise |
| Placebo | GMFR of Anti-SARS-CoV-2 S-protein IgG Antibody | 1.46 Fold Rise |
Secondary
GMT of Anti-SARS-CoV-2 S-protein Immunoglobulin G (IgG) Antibody
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S-268019-b | GMT of Anti-SARS-CoV-2 S-protein Immunoglobulin G (IgG) Antibody | 25209.25 Titer |
| Placebo | GMT of Anti-SARS-CoV-2 S-protein Immunoglobulin G (IgG) Antibody | 6.39 Titer |
Secondary
Number of Participants With First Occurrence of Asymptomatic SARS-CoV-2 Infection in the Initial Vaccination Period
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | Number of Participants With First Occurrence of Asymptomatic SARS-CoV-2 Infection in the Initial Vaccination Period | 2543 Participants |
| Placebo | Number of Participants With First Occurrence of Asymptomatic SARS-CoV-2 Infection in the Initial Vaccination Period | 1345 Participants |
Secondary
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period | 0 Participants |
| Placebo | Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Severe COVID-19 in the Initial Vaccination Period | 1 Participants |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | 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 | 0 Participants |
| Placebo | 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 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | 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 | 0 Participants |
| Placebo | 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 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | 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 | 0 Participants |
| Placebo | 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 |
Secondary
Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period
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.
Time frame: 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. 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period | 457 Participants |
| Placebo | Number of Participants With First Occurrence of SARS-CoV-2 RT-PCR-Positive Symptomatic COVID-19 in the Initial Vaccination Period | 313 Participants |
Secondary
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
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.
Time frame: 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. 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | 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 | 479 Participants |
| Placebo | 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 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-268019-b | 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 | 331 Participants |
| Placebo | 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 |
Secondary
Percentage of Participants Experiencing Solicited Local Adverse Events
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S-268019-b | Percentage of Participants Experiencing Solicited Local Adverse Events | 37.7 Percentage of Participants |
| Placebo | Percentage of Participants Experiencing Solicited Local Adverse Events | 14.6 Percentage of Participants |
Secondary
Percentage of Participants Experiencing Solicited Systemic Adverse Events
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S-268019-b | Percentage of Participants Experiencing Solicited Systemic Adverse Events | 32.7 Percentage of Participants |
| Placebo | Percentage of Participants Experiencing Solicited Systemic Adverse Events | 23.4 Percentage of Participants |
Secondary
Seroconversion Rate of Anti-SARS-CoV-2 S-protein IgG Antibody
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S-268019-b | Seroconversion Rate of Anti-SARS-CoV-2 S-protein IgG Antibody | 98.2 Percentage of Participants |
| Placebo | Seroconversion Rate of Anti-SARS-CoV-2 S-protein IgG Antibody | 7.1 Percentage of Participants |
Secondary
Seroconversion Rate of SARS-CoV-2 Neutralizing Antibody
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S-268019-b | Seroconversion Rate of SARS-CoV-2 Neutralizing Antibody | 93.1 Percentage of Participants |
| Placebo | Seroconversion Rate of SARS-CoV-2 Neutralizing Antibody | 3.6 Percentage of Participants |