Trial Outcomes & Findings for Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent Influenza Virus Vaccine (NCT NCT01946425)

NCT ID: NCT01946425

Last Updated: 2014-09-25

Results Overview

Solicited injection-site reactions (6 months to \<36 months of age): Tenderness, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Vomiting, Crying Abnormal, Drowsiness, Appetite loss, and Irritability. Grade 3: Tenderness, Cries if limb is moved; Erythema and Swelling, ≥50 mm; Fever, \>103.1ºF; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, \>3 hours; Drowsiness, Sleeping most of the time; Appetite lost, Refuses ≥3 feeds/meals or refuses most feeds/meals; Irritability, Inconsolable. Solicited injection-site reactions (3 years to \< 9 years of age): Pain, Erythema, and Swelling. Systemic Reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥50 mm; Fever, ≥102.1ºF; Headache, Malaise, and Myalgia, Significant, prevents daily activity.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

Day 0 up to Day 7 post-vaccination

Results posted on

2014-09-25

Participant Flow

The study participants were enrolled from 16 September 2013 to 10 October 2013 at 2 clinic centers in the United States.

A total of 60 participants who met all of the inclusion and none of the exclusion criteria were enrolled and vaccinated in this study.

Participant milestones

Participant milestones
Measure	Age 6 Months to <36 Months Group Participants 6 months to \<36 months of age who received a 0.25 mL dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group Participants 3 years to \<9 years of age who received a 0.5 mL dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)
Overall Study STARTED	30	30
Overall Study COMPLETED	28	30
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Age 6 Months to <36 Months Group Participants 6 months to \<36 months of age who received a 0.25 mL dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group Participants 3 years to \<9 years of age who received a 0.5 mL dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent Influenza Virus Vaccine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Age 6 to <36 Months Group n=30 Participants Participants 6 months to \<36 months of age who received a 0.25 mL dose of Fluzone® Quadrivalent Influenza Virus Vaccine (2013-2014 formulation)	Age 3 to <9 Years Group n=30 Participants Participants 3 years to \<9 years of age who received a 0.5 mL dose of Fluzone® Quadrivalent Influenza Virus Vaccine (2013-2014 formulation)	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous Age Continuous	1.9 Years STANDARD_DEVIATION 0.6 • n=5 Participants	5.4 Years STANDARD_DEVIATION 1.8 • n=7 Participants	3.7 Years STANDARD_DEVIATION 2.2 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	19 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 up to Day 7 post-vaccination

Population: Solicited injection-site reactions and systemic reactions were assessed using the Safety Analysis Set, which includes all participants who received at least one dose of study vaccine.

Outcome measures

Outcome measures
Measure	Age 6 Months to <36 Months Group n=29 Participants Participants 6 months to \<36 months of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group n=30 Participants Participants 3 years to \<9 years of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Appetite lost	7 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Malaise	NA Participants This systemic reaction was not solicited in this group.	11 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Injection-site tenderness	20 Participants	NA Participants This injection-site reaction was not solicited in this group
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Crying abnormal	3 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Drowsiness	8 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Drowsiness	1 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Appetite lost	2 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Irritability	17 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Injection-site tenderness	5 Participants	NA Participants This injection-site reaction was not solicited in this group
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Injection-site erythema	15 Participants	10 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Injection-site erythema	0 Participants	1 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Injection-site swelling	7 Participants	7 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Injection-site swelling	0 Participants	1 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Injection-site pain	NA Participants This injection-site reaction was not solicited in this group.	21 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Injection-site pain	NA Participants This injection-site reaction was not solicited in this group.	1 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Fever	6 Participants	2 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Fever	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Vomiting	4 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Vomiting	0 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Crying abnormal	10 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Irritability	3 Participants	NA Participants This systemic reaction was not solicited in this group.
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Headache	NA Participants This systemic reaction was not solicited in this group.	4 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Headache	NA Participants This systemic reaction was not solicited in this group.	1 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Malaise	NA Participants This systemic reaction was not solicited in this group.	0 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Myalgia	NA Participants This systemic reaction was not solicited in this group.	13 Participants
Number of Participants Reporting Solicited Injection-Site or Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine Grade 3 Myalgia	NA Participants This systemic reaction was not solicited in this group.	1 Participants

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 after final vaccination

Population: Geometric mean titers of antibodies against the hemagglutinin antigens were assessed in the Per-Protocol Analysis Set.

Influenza virus antibodies were measured using a hemagglutination inhibition (HAI) assay.

Outcome measures

Outcome measures
Measure	Age 6 Months to <36 Months Group n=26 Participants Participants 6 months to \<36 months of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group n=28 Participants Participants 3 years to \<9 years of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H1N1 (pre-vaccination; N = 25, 28)	14.1 Titers Interval 7.76 to 25.8	136 Titers Interval 68.4 to 271.0
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H1N1 (post-vaccination; N = 26, 28)	245 Titers Interval 132.0 to 455.0	1264 Titers Interval 930.0 to 1719.0
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H3N2 (pre-vaccination; N = 25, 28)	23.6 Titers Interval 12.5 to 44.8	215 Titers Interval 109.0 to 427.0
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H3N2 (post-vaccination; N = 26, 28)	484 Titers Interval 287.0 to 817.0	1103 Titers Interval 788.0 to 1544.0
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Yamagata (pre-vaccination; N = 25, 28)	6.24 Titers Interval 4.94 to 7.88	29.0 Titers Interval 18.3 to 45.8
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Yamagata (post-vaccination; N = 26, 28)	48.2 Titers Interval 26.7 to 87.1	162 Titers Interval 114.0 to 231.0
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Victoria (pre-vaccination; N = 25, 28)	5.99 Titers Interval 4.76 to 7.54	13.1 Titers Interval 8.61 to 20.0
Geometric Mean Titers (GMTs) of Influenza Antibodies Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Victoria (post-vaccination; N = 26, 28)	24.8 Titers Interval 12.7 to 48.1	113 Titers Interval 72.8 to 176.0

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 after final vaccination

Population: Seroprotection against the hemagglutinin antigens were assessed in the Per-Protocol Analysis Set.

Influenza virus antibodies were measured using an HAI assay. Seroprotection was defined as a titer ≥40 (1/dilution).

Outcome measures

Outcome measures
Measure	Age 6 Months to <36 Months Group n=26 Participants Participants 6 months to \<36 months of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group n=28 Participants Participants 3 years to \<9 years of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H1N1 (pre-vaccination; N = 25, 28)	5 Participants	19 Participants Interval 0.0 to 0.0
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H1N1 (post-vaccination; N = 26, 28)	22 Participants	28 Participants Interval 0.0 to 0.0
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H3N2 (pre-vaccination; N = 25, 28)	8 Participants	24 Participants Interval 0.0 to 0.0
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H3N2 (post-vaccination; N = 26, 28)	24 Participants	28 Participants Interval 0.0 to 0.0
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Yamagata (pre-vaccination; N = 25, 28)	1 Participants	16 Participants Interval 0.0 to 0.0
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Yamagata (post-vaccination; N = 26, 28)	18 Participants	27 Participants Interval 0.0 to 0.0
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Victoria (pre-vaccination; N = 25, 28)	1 Participants	6 Participants Interval 0.0 to 0.0
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Victoria (post-vaccination; N = 26, 28)	8 Participants	22 Participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 after final vaccination

Population: Seroconversion against the hemagglutinin antigens were assessed in the Per-Protocol Analysis Set.

Influenza virus antibodies were measured using an HAI assay. Seroconversion was defined as either a pre-vaccination HAI titer \< 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination titer.

Outcome measures

Outcome measures
Measure	Age 6 Months to <36 Months Group n=26 Participants Participants 6 months to \<36 months of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group n=28 Participants Participants 3 years to \<9 years of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)
Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Yamagata (N = 25, 28)	17 Participants	17 Participants Interval 0.0 to 0.0
Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Victoria (N = 25, 28)	8 Participants	17 Participants Interval 0.0 to 0.0
Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H1N1 (N = 25, 28)	20 Participants	19 Participants Interval 0.0 to 0.0
Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H3N2 (N = 25, 28)	22 Participants	14 Participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 after final vaccination

Population: Geometric mean titer ratios against the hemagglutinin antigens were assessed in the Per-Protocol Analysis Set.

Influenza virus antibodies were measured using an HAI assay. Geometric mean titer ratios are the geometric means of the individual post-vaccination/pre-vaccination titer ratios for each hemagglutinin antigen contained in the vaccine.

Outcome measures

Outcome measures
Measure	Age 6 Months to <36 Months Group n=26 Participants Participants 6 months to \<36 months of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group n=28 Participants Participants 3 years to \<9 years of age that received Fluzone® Quadrivalent, Influenza Vaccine (2013-2014 formulation)
Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H1N1 (N = 25, 28)	13.9 Titer Ratio Interval 8.33 to 23.3	8.83 Titer Ratio Interval 4.95 to 15.7
Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine A/H3N2 (N = 25, 28)	15.8 Titer Ratio Interval 9.43 to 26.4	4.82 Titer Ratio Interval 2.99 to 7.75
Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Yamagata (N = 25, 28)	5.13 Titer Ratio Interval 3.06 to 8.61	4.70 Titer Ratio Interval 3.2 to 6.9
Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Influenza Vaccine B Victoria (N = 25, 28)	2.87 Titer Ratio Interval 1.72 to 4.79	6.17 Titer Ratio Interval 4.17 to 9.13

Adverse Events

Age 6 Months to <36 Months Group

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Age 3 Years to <9 Years Group

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director

Sanofi Pasteur Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications
Publication restrictions are in place

Restriction type: OTHER

Measure	Age 6 Months to <36 Months Group n=30 participants at risk Participants 6 months to \< 36 months of age that received Fluzone® Quadrivalent Influenza Vaccine (2013-2014 formulation)	Age 3 Years to <9 Years Group n=30 participants at risk Participants age 3 years to \< 9 years of age that received Fluzone® Quadrivalent Influenza Vaccine (2013-2014 formulation)
Gastrointestinal disorders Diarrhoea	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	3.3% 1/30 • Number of events 1 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Infections and infestations Croup infectious	3.3% 1/30 • Number of events 1 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Infections and infestations Sinusitis	0.00% 0/30 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Infections and infestations Upper respiratory tract infection	23.3% 7/30 • Number of events 8 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	6.7% 2/30 • Number of events 3 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 3/30 • Number of events 3 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	3.3% 1/30 • Number of events 1 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	10.0% 3/30 • Number of events 3 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
General disorders Injection-site tenderness	69.0% 20/29 • Number of events 20 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
General disorders Injection-site erythema	51.7% 15/29 • Number of events 15 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	33.3% 10/30 • Number of events 10 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
General disorders Injection-site swelling	24.1% 7/29 • Number of events 7 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	23.3% 7/30 • Number of events 7 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
General disorders Fever	20.7% 6/29 • Number of events 6 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Gastrointestinal disorders Vomiting	13.8% 4/29 • Number of events 4 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Psychiatric disorders Crying abnormal	34.5% 10/29 • Number of events 10 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Nervous system disorders Drowsiness	27.6% 8/29 • Number of events 8 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Metabolism and nutrition disorders Appetite lost	24.1% 7/29 • Number of events 7 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Psychiatric disorders Irritability	58.6% 17/29 • Number of events 17 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
General disorders Injection-site pain	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	70.0% 21/30 • Number of events 21 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Nervous system disorders Headache	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	13.3% 4/30 • Number of events 4 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
General disorders Malaise	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	36.7% 11/30 • Number of events 11 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.
Musculoskeletal and connective tissue disorders Myalgia	— 0/0 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.	43.3% 13/30 • Number of events 13 • Adverse event data were collected from Day 0 (post-vaccination) up to Day 28 after final vaccination.