Trial Outcomes & Findings for Safety and Immunogenicity of the 2015-2016 Formulation of Fluzone® Quadrivalent (Influenza Vaccine) Among Healthy Children (NCT NCT02539108)

Last Updated: 2016-11-29

Results Overview

Solicited injection-site reactions for 6 to \< 36 months: Tenderness, Erythema, and Swelling. For 3 to \< 9 years: Pain, Erythema, and Swelling. Solicited systemic reactions for 6 to \< 36 months: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. For 3 to \< 9 years: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 for 6 to \< 36 months: Tenderness, Cries when injected limb is moved; Erythema and Swelling, ≥ 50 mm; Vomiting, 6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, \> 3 hours; Drowsiness, sleeping most of the time or difficult to wake up; Appetite lost, Refuses ≥ 3 feeds/meals or refuses most feeds/meals; and Irritability, Inconsolable. Grade 3 for 3 to \< 9 years: Pain, Incapacitating; Erythema and Swelling, ≥ 50 mm; Fever, ≥ 39.0°C; Headache, Malaise, and Myalgia, prevents daily activity.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

Day 0 up to Day 7 post any vaccination

Results posted on

2016-11-29

Participant Flow

Study participants were enrolled from 31 August 2015 to 30 November 2015 at 2 clinic centers in the United States.

A total of 60 participants who met all inclusion and no exclusion criteria were enrolled and vaccinated.

Participant milestones

Participant milestones
Measure	6 to <36 Months of Age Children 6 to \<36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age Children 3 to \<9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Overall Study STARTED	30	30
Overall Study COMPLETED	30	30
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Immunogenicity of the 2015-2016 Formulation of Fluzone® Quadrivalent (Influenza Vaccine) Among Healthy Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	6 to <36 Months of Age n=30 Participants Children 6 to \<36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 Participants Children 3 to \<9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	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	21.9 Months STANDARD_DEVIATION 8.59 • n=5 Participants	72.0 Months STANDARD_DEVIATION 22.9 • n=7 Participants	46.9 Months STANDARD_DEVIATION 30.50 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	16 Participants n=7 Participants	26 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 any vaccination

Population: Solicited injection-site and systemic reactions were assessed in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure	6 to <36 Months of Age n=30 Participants Children 6 to \<36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 Participants Children 3 to \<9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Appetite lost	0 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Injection-Site Tenderness (N=30, 0)	21 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Injection-Site Tenderness	0 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Injection-Site Pain (N=0, 30)	NA Participants Event was not assessed in this group	16 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Injection-site Pain	NA Participants Event was not assessed in this group	0 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Injection-Site Erythema	11 Participants	11 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Injection-Site Erythema	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Injection-Site Swelling	3 Participants	8 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Injection-Site Swelling	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Fever	4 Participants	2 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Fever	0 Participants	2 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Vomiting (N=30, 0)	1 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Vomiting	0 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Crying abnormal (N=30, 0)	9 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Crying abnormal	0 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Drowsiness (N=30, 0)	8 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Drowsiness	0 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Appetite lost (N=30, 0)	9 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Irritability (N=30, 0)	15 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Irritability	0 Participants	NA Participants Event was not assessed in this group
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Headache (N=0, 30)	NA Participants Event was not assessed in this group	2 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Headache	NA Participants Event was not assessed in this group	0 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Malaise(N=0, 30)	NA Participants Event was not assessed in this group	6 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Malaise	NA Participants Event was not assessed in this group	0 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Myalgia (N=0, 30)	NA Participants Event was not assessed in this group	10 Participants
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine. Grade 3 Myalgia	NA Participants Event was not assessed in this group	0 Participants

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and 28 days post-last vaccination

Population: Anti-influenza antibody titers were assessed in the Per-protocol Analysis Set.

Anti-influenza antibodies were measured using an hemagglutination inhibition assay.

Outcome measures

Outcome measures
Measure	6 to <36 Months of Age n=30 Participants Children 6 to \<36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 Participants Children 3 to \<9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H1N1; Pre-vaccination	14.8 Titers (1/dilutions) Interval 8.6 to 25.5	184 Titers (1/dilutions) Interval 85.3 to 396.0
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H1N1; Post-vaccination	288 Titers (1/dilutions) Interval 167.0 to 498.0	937 Titers (1/dilutions) Interval 625.0 to 1406.0
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H3N2; Pre-vaccination	28.9 Titers (1/dilutions) Interval 13.5 to 62.0	139 Titers (1/dilutions) Interval 79.8 to 243.0
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H3N2; Post-vaccination	1140 Titers (1/dilutions) Interval 576.0 to 2259.0	3263 Titers (1/dilutions) Interval 2255.0 to 4721.0
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Yamagata; Pre-vaccination	16.2 Titers (1/dilutions) Interval 10.7 to 24.7	113 Titers (1/dilutions) Interval 64.3 to 199.0
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Yamagata; Post-vaccination	408 Titers (1/dilutions) Interval 257.0 to 646.0	1028 Titers (1/dilutions) Interval 659.0 to 1604.0
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Victoria; Pre-vaccination	14.0 Titers (1/dilutions) Interval 8.35 to 23.4	108 Titers (1/dilutions) Interval 54.1 to 216.0
Geometric Mean Titers of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Victoria; Post-vaccination	339 Titers (1/dilutions) Interval 207.0 to 555.0	718 Titers (1/dilutions) Interval 462.0 to 1118.0

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and 28 days post-last vaccination

Population: Anti-influenza antibody titers were assessed in the Per-Protocol Analysis Set.

Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Seroprotection was defined as a pre-vaccination or post-vaccination influenza antibody titer of ≥ 1:40 (1/dilutions).

Outcome measures

Outcome measures
Measure	6 to <36 Months of Age n=30 Participants Children 6 to \<36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 Participants Children 3 to \<9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H1N1; Pre-vaccination	10 Participants	22 Participants
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H1N1; Post-vaccination	28 Participants	30 Participants
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H3N2; Pre-vaccination	14 Participants	26 Participants
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H3N2; Post-vaccination	29 Participants	30 Participants
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Yamagata; Pre-vaccination	8 Participants	23 Participants
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Yamagata; Post-vaccination	29 Participants	30 Participants
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Victoria; Pre-vaccination	7 Participants	20 Participants
Number of Participants Who Achieved Seroprotection to Influenza Virus Antigens Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Victoria; Post-vaccination	28 Participants	30 Participants

SECONDARY outcome

Timeframe: 28 days post-last vaccination

Population: Anti-influenza antibody titers were assessed in the Per-Protocol Analysis Set.

Anti-influenza antibodies were measured using an hemagglutination inhibition (HAI) assay. Seroconversion was defined as either a pre-vaccination HAI titer \< 1:10 and a post-final vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a four-fold increase in post-final vaccination titer.

Outcome measures

Outcome measures
Measure	6 to <36 Months of Age n=30 Participants Children 6 to \<36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 Participants Children 3 to \<9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Number of Participants Who Achieved Seroconversion Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H1N1	24 Participants	15 Participants
Number of Participants Who Achieved Seroconversion Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H3N2	28 Participants	28 Participants
Number of Participants Who Achieved Seroconversion Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Yamagata	28 Participants	24 Participants
Number of Participants Who Achieved Seroconversion Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Victoria	27 Participants	21 Participants

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and 28 days post-last vaccination

Population: Anti-influenza antibody titers were assessed in the Per-protocol Analysis Set.

Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Geometric mean of titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer ratios

Outcome measures

Outcome measures
Measure	6 to <36 Months of Age n=30 Participants Children 6 to \<36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 Participants Children 3 to \<9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Geometric Mean Titer Ratios of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Yamagata	21.1 Titer ratio Interval 13.5 to 32.9	8.67 Titer ratio Interval 5.76 to 13.1
Geometric Mean Titer Ratios of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H1N1	13.0 Titer ratio Interval 7.63 to 22.1	4.59 Titer ratio Interval 2.93 to 7.21
Geometric Mean Titer Ratios of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine A/H3N2	28.2 Titer ratio Interval 17.0 to 46.8	22.9 Titer ratio Interval 15.0 to 34.9
Geometric Mean Titer Ratios of Influenza Virus Antibodies Following Vaccination With the 2015-2016 Formulation of Fluzone® Quadrivalent Influenza Vaccine B Victoria	17.3 Titer ratio Interval 10.8 to 28.0	6.35 Titer ratio Interval 4.17 to 9.66

Adverse Events

6 to <36 Months of Age

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

3 to <9 Years of Age

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	6 to <36 Months of Age n=30 participants at risk Children 6 to \< 36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 participants at risk Children 3 to \< 9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Skin and subcutaneous tissue disorders Linear IgA disease	3.3% 1/30 • Number of events 1 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.

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	6 to <36 Months of Age n=30 participants at risk Children 6 to \< 36 months of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.	3 to <9 Years of Age n=30 participants at risk Children 3 to \< 9 years of age received 1 intramuscular dose of Fluzone Quadrivalent Vaccine. A second dose was administered 28 days after the first vaccination in participants for whom a second dose was recommended according to Advisory Committee on Immunization Practices guidelines.
Gastrointestinal disorders Diarrhoea	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	3.3% 1/30 • Number of events 1 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Gastrointestinal disorders Teething	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Infections and infestations Otitis media acute	10.0% 3/30 • Number of events 3 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Infections and infestations Upper respiratory tract infection	16.7% 5/30 • Number of events 7 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 3/30 • Number of events 3 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Skin and subcutaneous tissue disorders Dermatitis diaper	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
General disorders Injection site Tenderness / Pain	70.0% 21/30 • Number of events 21 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	53.3% 16/30 • Number of events 16 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
General disorders Injection site Erythema	36.7% 11/30 • Number of events 11 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	36.7% 11/30 • Number of events 11 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
General disorders Injection site Swelling	10.0% 3/30 • Number of events 3 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	26.7% 8/30 • Number of events 8 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
General disorders Fever	13.3% 4/30 • Number of events 4 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Psychiatric disorders Crying abnormal	30.0% 9/30 • Number of events 9 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Nervous system disorders Drowsiness	26.7% 8/30 • Number of events 8 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Metabolism and nutrition disorders Appetite lost	30.0% 9/30 • Number of events 9 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Psychiatric disorders Irritability	50.0% 15/30 • Number of events 15 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Nervous system disorders Headache	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	6.7% 2/30 • Number of events 2 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
General disorders Malaise	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	20.0% 6/30 • Number of events 6 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/30 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.	33.3% 10/30 • Number of events 10 • Adverse event data were collected from Day 0 up to 28 days following the last vaccination.