Trial Outcomes & Findings for A Study of an Investigational Zoster Vaccine in Subjects With a History of Varicella (Chickenpox) Given Concomitantly With Another Vaccine (V211-011) (NCT NCT00231816)

Last Updated: 2015-09-21

Results Overview

The Geometric mean titer (GMT) of the VZV glycoprotein enzyme-linked immunosorbent assay (gpELISA) antibody responses at Week 4 postvaccination in participants who received ZOSTAVAX™ concomitantly with influenza vaccine was compared to that in subjects who received influenza vaccine and ZOSTAVAX™ nonconcomitantly.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

763 participants

Primary outcome timeframe

4 weeks

Results posted on

2015-09-21

Participant Flow

Participants were recruited at 13 sites in the United States and 7 sites in Europe. First Patient In (FPI): 23-SEP-2005; Last Patient Last Visit (LPLV): 08-MAR-2006

Participant milestones

Participant milestones
Measure	Concomitant Group ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
Overall Study STARTED	382	381
Overall Study Vaccinated at Visit 1	382	380
Overall Study Vaccinated at Visit 2	369	371
Overall Study COMPLETED	366	369
Overall Study NOT COMPLETED	16	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Concomitant Group ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	8	5
Overall Study Protocol Violation	2	3
Overall Study Withdrawal by Subject	3	3
Overall Study Other	2	1

Baseline Characteristics

A Study of an Investigational Zoster Vaccine in Subjects With a History of Varicella (Chickenpox) Given Concomitantly With Another Vaccine (V211-011)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Concomitant Group n=382 Participants ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group n=380 Participants Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4	Total n=762 Participants Total of all reporting groups
Age, Continuous	63.4 years STANDARD_DEVIATION 7.99 • n=5 Participants	63.6 years STANDARD_DEVIATION 8.24 • n=7 Participants	63.5 years STANDARD_DEVIATION 8.11 • n=5 Participants
Sex: Female, Male Female	215 Participants n=5 Participants	212 Participants n=7 Participants	427 Participants n=5 Participants
Sex: Female, Male Male	167 Participants n=5 Participants	168 Participants n=7 Participants	335 Participants n=5 Participants
Race/Ethnicity, Customized African	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Black	106 participants n=5 Participants	100 participants n=7 Participants	206 participants n=5 Participants
Race/Ethnicity, Customized Hispanic American	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Race/Ethnicity, Customized Indian	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Multiracial	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Native American	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White	258 participants n=5 Participants	261 participants n=7 Participants	519 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: The primary analysis was based on the per protocol population defined as participants who had valid GMT results from samples obtained within the prespecified day ranges at Day 1, at Week 4, or at Week 8 postvaccination, and who did not meet any of the protocol violations prespecified in the statistical analysis plan (SAP).

Outcome measures

Outcome measures
Measure	Concomitant Group n=361 Participants ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group n=366 Participants Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
Varicella-zoster Virus (VZV) Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Antibody Responses	553.5 gpELISA units/mL Interval 499.0 to 613.9	588.7 gpELISA units/mL Interval 531.9 to 651.5

OTHER_PRE_SPECIFIED outcome

Timeframe: prevaccination to 4 weeks postvaccination

Population: The analysis was based on the per protocol population defined as participants who had valid GMFR results from samples obtained within the prespecified day ranges at Day 1, at Week 4, or at Week 8 postvaccination, and who did not meet any of the protocol violations prespecified in the statistical analysis plan (SAP)

GMFR of the VZV gpELISA antibody titers from prevaccination to 4 weeks postvaccination when ZOSTAVAX™ is administered concomitantly with influenza vaccine

Outcome measures

Outcome measures
Measure	Concomitant Group n=354 Participants ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
Geometric Mean Fold Rise (GMFR) in VZV gpELISA Antibody Titers From Prevaccination to 4 Weeks Postvaccination	2.1 ratio Interval 2.0 to 2.3	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks postvaccination

Population: The analysis was based on the per protocol population defined as participants who had valid results from samples obtained within the prespecified day ranges at Day 1, at Week 4, or at Week 8 postvaccination, and who did not meet any of the protocol violations prespecified in the SAP.

GMT of the H1N1 strain antibody responses at 4 weeks postvaccination in participants who receive ZOSTAVAX™ concomitantly with influenza vaccine and those who receive ZOSTAVAX™ and influenza vaccine nonconcomitantly

Outcome measures

Outcome measures
Measure	Concomitant Group n=363 Participants ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group n=363 Participants Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
Geometric Mean Titers (GMTs) of H1N1 Strain Antibody Responses at 4 Weeks Postvaccination	122.9 titers Interval 107.8 to 140.0	134.2 titers Interval 118.3 to 152.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks postvaccination

GMT of the H3N2 strain antibody responses at 4 weeks postvaccination in participants who receive ZOSTAVAX™ concomitantly with influenza vaccine and those who receive ZOSTAVAX™ and influenza vaccine nonconcomitantly

Outcome measures

Outcome measures
Measure	Concomitant Group n=363 Participants ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group n=363 Participants Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
GMTs of H3N2 Strain Antibody Responses at 4 Weeks Postvaccination	162.7 titers Interval 140.4 to 188.4	150.5 titers Interval 129.8 to 174.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks postvaccination

GMT of the B strain antibody responses at 4 weeks postvaccination in participants who receive ZOSTAVAX™ concomitantly with influenza vaccine and those who receive ZOSTAVAX™ and influenza vaccine nonconcomitantly

Outcome measures

Outcome measures
Measure	Concomitant Group n=363 Participants ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group n=363 Participants Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
GMTs of B Strain Antibody Responses at 4 Weeks Postvaccination	119.8 titers Interval 104.8 to 137.1	136.5 titers Interval 120.5 to 154.7

Adverse Events

Concomitant Group

Serious events: 6 serious events

Other events: 199 other events

Deaths: 0 deaths

Nonconcomitant Group

Serious events: 5 serious events

Other events: 181 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Concomitant Group n=378 participants at risk ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group n=376 participants at risk Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
Infections and infestations Upper respiratory tract infection	5.0% 19/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	4.5% 17/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Erythema (Influenza vaccine injection site)	12.2% 46/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	7.7% 29/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Erythema (Placebo injection site)	2.9% 11/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	5.1% 19/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Erythema (ZOSTAVAX™ injection site)	33.1% 125/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	26.9% 101/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Pain (Influenza vaccine injection site)	23.8% 90/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	22.9% 86/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Pain (Placebo injection site)	4.2% 16/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	6.1% 23/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Pain (ZOSTAVAX™ injection site)	30.2% 114/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	28.5% 107/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Swelling (Influenza vaccine injection site)	10.8% 41/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	8.2% 31/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
General disorders Injection Site Swelling (ZOSTAVAX™ injection site)	18.5% 70/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	25.0% 94/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Concomitant Group n=378 participants at risk ZOSTAVAX™ 0.65 mL subcutaneous (SC) injection administered concomitantly with 0.5 mL intramuscular (IM) influenza vaccine injection at separate injection sites on Day 1 and placebo injection at Week 4	Nonconcomitant Group n=376 participants at risk Influenza vaccine 0.5 mL IM injection administerd with placebo injection on Day 1 and ZOSTAVAX™ 0.65 mL SC injection at Week 4
Blood and lymphatic system disorders Anaemia	0.00% 0/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.27% 1/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Cardiac disorders Angina unstable	0.00% 0/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.27% 1/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Cardiac disorders Aortic valve stenosis	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Cardiac disorders Arrhythmia	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Cardiac disorders Cardiac failure congestive	0.79% 3/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Cardiac disorders Myocardial infarction	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Infections and infestations Appendicitis	0.00% 0/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.27% 1/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Infections and infestations Pneumonia	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.27% 1/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.27% 1/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Nervous system disorders Convulsion	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.26% 1/378 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis	0.00% 0/376 • Day 1-28 following each vaccination Injection-site adverse events (AEs), rashes, oral temperatures (if the subject felt febrile), and other AEs were recorded by the participant on a Vaccination Report Card which was reviewed by the study site personnel at the end of each 28-day follow-up period. 4 participants from each group were lost to follow up \& not included in the analysis