SA4Ag Safety, Tolerability, and Immunogenicity Study in Japanese Adults

Percentage of participants achieving predefined antibody response to capsular polysaccharide serotype 5 (CP5), capsular polysaccharide serotype 8 (CP8), clumping factor A (ClfA) and manganese transporter C (MntC) at Day 29 were reported. The predefined thresholds for the target antigens were 1000 and 2000 based on opsonophagocytic activity (OPA) assay for CP5 and CP8, respectively; was 121 based on fibrinogen-binding inhibition (FBI) assay for ClfA and 512 based on competitive Luminex immunoassay (cLIA) for MntC.

Time frame: Day 29

Population: The evaluable immunogenicity population included all participants who received investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for primary immunogenicity analysis. Here n signifies the number of participants who were evaluable for specific antigens for each arm, respectively.

Local reactions were recorded using an electronic daily diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were defined as mild (2.5 to 5.0 centimeters \[cm\]), moderate (5.5 to 10.0 cm) and, severe (greater than or equal to \[\>=\] 10.5 cm). Pain at injection site was defined as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). In this outcome measure percentage of participants with any local reaction was reported.

Time frame: Day 1 up to Day 14

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination.

Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 37.5 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and greater than (\>) 40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (\>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (significant, prevented daily activity). In this outcome measure percentage of participants with any systemic event was reported.

Time frame: Day 1 up to Day 14

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination.

Blood chemistry laboratory analysis included the following parameters: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, creatinine, creatine kinase and lactate dehydrogenase, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Blood chemistry abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in blood chemistry laboratory parameters are reported in this outcome measure.

Time frame: Day 15

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination. Here N signifies number of participants who were evaluable for this outcome measure.

Blood chemistry laboratory analysis included the following parameters: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, creatinine, creatine kinase and lactate dehydrogenase, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Blood chemistry abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in blood chemistry laboratory parameters are reported in this outcome measure.

Time frame: Day 5

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination. Here N signifies number of participants who were evaluable for this outcome measure.

Coagulation analysis included the following parameters: PT, APTT, platelet AGG with ADP, platelet AGG with arachidonic acid, platelet AGG with collagen and fibrinogen activity. PT and APTT were scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Coagulation abnormality was defined as at least 1 grade abnormal value for PT and APTT, and deviation from local laboratory range for platelet aggregation assay and fibrinogen activity assay. Percentage of participants with abnormal values in coagulation parameters are reported in this outcome measure.

Time frame: Day 15

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination. Here N signifies number of participants who were evaluable for this outcome measure.

Coagulation analysis included the following parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation (AGG) (with adenosine diphosphate \[ADP\], with arachidonic acid, and with collagen) and fibrinogen activity. PT and APTT were scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Coagulation abnormality was defined as at least 1 grade abnormal value for PT and APTT, and deviation from local laboratory range for platelet aggregation assay and fibrinogen activity assay. Percentage of participants with abnormal values in coagulation parameters are reported in this outcome measure.

Time frame: Day 5

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination. Here N signifies number of participants who were evaluable for this outcome measure.

Hematology analysis included the following parameters: hemoglobin, white blood cells, neutrophils and platelets, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Hematology abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in hematology parameters are reported in this outcome measure.

Time frame: Day 15

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination. Here N signifies number of participants who were evaluable for this outcome measure.

Hematology analysis included the following parameters: hemoglobin, white blood cells, neutrophils and platelets, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Hematology abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in hematology parameters are reported in this outcome measure.

Time frame: Day 5

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination. Here 'number of participants analyzed (N)' signifies number of participants who were evaluable for this outcome measure.

Local reactions were recorded using an electronic daily diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (2.5 to 5.0 cm), moderate (5.5 to 10.0 cm) and, severe (\>=10.5 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity).

Time frame: Day 1 up to Day 14

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination.

Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 37.5 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and \>40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (\>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (significant, prevented daily activity).

Time frame: Day 1 up to Day 14

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or deemed medically significant for any other reason. A treatment emergent AE was defined as an event that emerged during the study that was absent before administration of investigational product, or worsened relative to the pre-administration state. AEs reported during this time period included both SAEs and newly diagnosed chronic medical disorders (NDCMD). A NDCMD was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.

Time frame: After Day 29 up to Month 12

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious AEs. Treatment-emergent AEs were events between the administration of investigational product and up to Day 29 that were absent before vaccination or that worsened relative to pre-administration state.

Time frame: Day 1 up to Day 29

Population: Safety population included all participants who received at least 1 dose of investigational product and had safety data available after vaccination.

Geometric mean titer is commonly used to assess the immunogenicity of vaccine. Antibody GMTs as measured by cLIA for ClfA and MntC and corresponding 2-sided 95 percent (%) confidence intervals (CIs) were evaluated. CIs were computed by back transforming the CIs generated for means of the titers on the log scale based on the Student t distribution.

Time frame: Baseline, Day 11, 15, 29 and Month 3

Population: The evaluable immunogenicity population included all participants who received the investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for the primary immunogenicity analysis.

Geometric mean titer is commonly used to assess the immunogenicity of vaccine. Antibody GMTs as measured by FBI for ClfA and corresponding 2-sided 95 percent CIs were evaluated. CIs were computed by back transforming the CIs generated for means of the titers on the log scale based on the Student t distribution.

Time frame: Baseline, Day 11, 15, 29 and Month 3

Population: The evaluable immunogenicity population included all participants who received the investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for the primary immunogenicity analysis.

Geometric mean titer is commonly used to assess the immunogenicity of vaccine. Antibody GMTs as measured by OPA for CP5 and CP8 and corresponding 2-sided 95 percent CIs were evaluated. CIs were computed by back transforming the CIs generated for means of the titers on the log scale based on the Student t distribution.

Time frame: Baseline, Day 11, 15, 29 and Month 3

Population: The evaluable immunogenicity population included all participants who received the investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for primary immunogenicity analysis. Here n signifies number of participants who were evaluable for specific antigens for each arm, respectively.

GMFRs of anti-Staphylococcus aureus cLIA for ClfA and MntC were computed. CIs which are reported below were computed by back transforming the CIs generated for the mean fold rise on the log scale based on the Student t distribution. GMFRs were computed as the fold rise in titer value at specified time point compared to baseline.

Time frame: Baseline, Day 11, 15, 29 and Month 3

Population: The evaluable immunogenicity population included all participants who received the investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for the primary immunogenicity analysis.

GMFR of anti-Staphylococcus aureus FBI for ClfA was computed. CIs which are reported below were computed by back transforming the CIs generated for the mean fold rise on the log scale based on the Student t distribution. GMFRs were computed as the fold rise in titer value at specified time point compared to baseline.

Time frame: Baseline, Day 11, 15, 29 and Month 3

Population: The evaluable immunogenicity population included all participants who received the investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for the primary immunogenicity analysis.

GMFRs of anti-Staphylococcus aureus OPA for CP5 and CP8 were computed. CIs which are reported below were computed by back transforming the CIs generated for the mean fold rise on the log scale based on the Student t distribution. GMFRs were computed as the fold rise in titer value at specified time point compared to baseline.

Time frame: Baseline, Day 11, 15, 29 and Month 3

Population: The evaluable immunogenicity population included all participants who received the investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for primary immunogenicity analysis. Here n signifies number of participants who were evaluable for specific antigens for each arm, respectively.

Percentage of participants achieving predefined antibody response to CP5, CP8, ClfA and MntC at Baseline, Day 11, 15 and Month 3 were reported. The predefined thresholds for the target antigens were 1000 and 2000 based on OPA assay for CP5 and CP8, respectively; was 121 based on FBI assay for ClfA, 512 based on cLIA for MntC.

Time frame: Baseline, Day 11, 15 and Month3

Population: The evaluable immunogenicity population included all participants who received investigational product to which they were randomized, had valid and determinate assay result for at least 1 antigen for primary immunogenicity analysis. Here n signifies the number of participants who were evaluable for specific antigens for each arm, respectively.