Trial Outcomes & Findings for A Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK)'s Infanrix Hexa Vaccine (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis Vaccine (DTaP5-HBV-IPV-Hib) in Healthy Infants and Toddlers (NCT NCT04535037)

Last Updated: 2024-08-27

Results Overview

Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in microgram per milliliter (μg/mL), as assessed by Enzyme-linked immunosorbent assay (ELISA).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

500 participants

Primary outcome timeframe

At Month 11 (i.e., 1-month post-booster vaccination)

Results posted on

2024-08-27

Participant Flow

Participant milestones

Participant milestones
Measure	Infanrix Hexa All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Overall Study STARTED	249	251
Overall Study COMPLETED	237	233
Overall Study NOT COMPLETED	12	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Infanrix Hexa All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	8	9
Overall Study Migrated / moved from the study area	1	4
Overall Study Other	2	5

Baseline Characteristics

A Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK)'s Infanrix Hexa Vaccine (DTPa-HBV-IPV/Hib) Versus MCM Vaccine BV's Vaxelis Vaccine (DTaP5-HBV-IPV-Hib) in Healthy Infants and Toddlers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Infanrix Hexa n=249 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=251 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Total n=500 Participants Total of all reporting groups
Age, Continuous	8.6 Weeks STANDARD_DEVIATION 1.17 • n=5 Participants	8.6 Weeks STANDARD_DEVIATION 1.24 • n=7 Participants	8.6 Weeks STANDARD_DEVIATION 1.20 • n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	135 Participants n=7 Participants	240 Participants n=5 Participants
Sex: Female, Male Male	144 Participants n=5 Participants	116 Participants n=7 Participants	260 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central / South Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic / North African Heritage	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized White - Caucasian / European Heritage	236 Participants n=5 Participants	235 Participants n=7 Participants	471 Participants n=5 Participants
Race/Ethnicity, Customized Other-Unspecified	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Month 11 (i.e., 1-month post-booster vaccination)

Population: The analysis was performed on the Per Protocol Set (PPS), which included all eligible subjects who received diphtheria, tetanus and acellular pertussis (DTPa)-combination study vaccines as per protocol, who had anti-PRP results post-vaccination, who complied with vaccination/blood draw intervals, without intercurrent conditions and without prohibited concomitant medication/vaccination and for whom immunogenicity data were available for specific timepoints.

Anti-PRP antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in microgram per milliliter (μg/mL), as assessed by Enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=211 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=218 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations at Month 11, Based on Per Protocol Set (PPS)	11.61 μg/mL As specified in the Statistical Analysis Plan, for the co-primary objectives, only geometric mean was calculated for anti-PRP antibody concentration and was adjusted for DTPa vaccination of the mother.	12.66 μg/mL As specified in the Statistical Analysis Plan, for the co-primary objectives, only geometric mean was calculated for anti-PRP antibody concentration and was adjusted for DTPa vaccination of the mother.

PRIMARY outcome

Timeframe: At Month 11 (i.e., 1-month post-booster vaccination)

Population: The analysis was performed on PPS, which included all eligible subjects who received all DTPa-combination study vaccines as per protocol, who had anti-PRP results post-vaccination, who complied with vaccination/blood draw intervals, without intercurrent conditions and without prohibited concomitant medication/vaccination and for whom immunogenicity data were available for specific timepoints.

The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=211 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=218 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Percentage of Subjects With Anti-PRP Antibody Concentrations Equal to or Above (≥) 5 µg/mL at Month 11, Based on PPS	75.4 Percentage of Participants	81.7 Percentage of Participants

PRIMARY outcome

Timeframe: At Month 11 (i.e., 1-month post-booster vaccination)

Population: The analysis was performed on the Exposed Set (ES), which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1 and for whom immunogenicity data were available for specific timepoints.

Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=175 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=228 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Anti-PRP Antibody Concentrations at Month 11, Based on the Exposed Set (ES)	11.26 μg/mL As specified in the Statistical Analysis Plan, for the co-primary objectives, only geometric mean was calculated for anti-PRP antibody concentration and was adjusted for DTPa vaccination of the mother.	12.85 μg/mL As specified in the Statistical Analysis Plan, for the co-primary objectives, only geometric mean was calculated for anti-PRP antibody concentration and was adjusted for DTPa vaccination of the mother.

PRIMARY outcome

Timeframe: At Month 11 (i.e., 1-month post-booster vaccination)

Population: The analysis was performed on the ES, which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1 and for whom immunogenicity data were available for specific timepoints.

The percentage of subjects with anti-PRP antibody concentrations ≥5 µg/mL was reported, as assessed by ELISA.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=175 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=186 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 5 µg/mL at Month 11, Based on ES	75.4 Percentage of Participants	81.6 Percentage of Participants

SECONDARY outcome

Timeframe: At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination)

The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold for short-term protection was reported. The threshold for short-term protection is 0.15 µg/mL.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=213 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=230 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL At month 3	79.8 Percentage of Participants Interval 73.79 to 84.99	100 Percentage of Participants Interval 98.41 to 100.0
Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL At Month 10	61.2 Percentage of Participants Interval 54.14 to 67.86	94.4 Percentage of Participants Interval 90.5 to 97.1
Percentage of Subjects With Anti-PRP Antibody Concentration ≥ 0.15 µg/mL At Month 11	99.5 Percentage of Participants Interval 97.39 to 99.99	99.5 Percentage of Participants Interval 97.47 to 99.99

SECONDARY outcome

Timeframe: At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination)

The percentage of subjects with anti-PRP antibody concentration equal to or above the threshold for long-term protection was reported. The threshold for long-term protection is 1.0 µg/mL.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=213 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=230 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL At Month 3	30.5 Percentage of Participants Interval 24.41 to 37.18	92.2 Percentage of Participants Interval 87.91 to 95.3
Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL At Month 10	13.1 Percentage of Participants Interval 8.82 to 18.49	69.0 Percentage of Participants Interval 62.35 to 75.08
Percentage of Subjects With Anti-PRP Antibody Concentrations ≥ 1.0 µg/mL At Month 11	97.2 Percentage of Participants Interval 93.91 to 98.95	94.5 Percentage of Participants Interval 90.58 to 97.12

SECONDARY outcome

Timeframe: At Month 3 (i.e., 1-month post-primary vaccination), Month 10 (i.e., pre-booster) and Month 11 (i.e., 1-month post-booster vaccination)

Anti-PRP antibody concentrations were presented as GMCs and expressed in μg/mL, as assessed by ELISA.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=213 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=230 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Anti-PRP Antibody Concentrations At Month 3	0.5 μg/mL Interval 0.41 to 0.62	11.3 μg/mL Interval 9.35 to 13.6
Anti-PRP Antibody Concentrations At Month 10	0.2 μg/mL Interval 0.19 to 0.28	1.9 μg/mL Interval 1.56 to 2.26
Anti-PRP Antibody Concentrations At Month 11	12.0 μg/mL Interval 9.96 to 14.34	12.9 μg/mL Interval 10.75 to 15.55

SECONDARY outcome

Timeframe: During the 31-day (Days 1-31) follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age)

Population: The analysis was performed on the ES, which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1.

AEs are defined as any untoward medical occurrence in a subject or subjects, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=249 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=251 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Number of Subjects With Unsolicited Adverse Events (AEs)	178 Participants	199 Participants

SECONDARY outcome

Timeframe: Throughout the entire period of the study (from Day 1 up to study end [Month 11])

Population: The analysis was performed on the ES, which included all vaccinated subjects who were analysed according to the intervention they received at Dose 1.

A SAEs is defined as any untoward medical occurrence that, at any dose, result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Infanrix Hexa n=249 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=251 Participants All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Number of Subjects With Serious Adverse Events (SAEs)	14 Participants	10 Participants

Adverse Events

Infanrix Hexa

Serious events: 14 serious events

Other events: 178 other events

Deaths: 0 deaths

Vaxelis

Serious events: 10 serious events

Other events: 199 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK 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	Infanrix Hexa n=249 participants at risk All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTPa-HBV-IPV/Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.	Vaxelis n=251 participants at risk All subjects in this group received 3 doses (2 primary doses and 1 booster dose) of DTaP5 HBV IPV Hib vaccine co-administered with 3 doses of pneumococcal 13 valent conjugate vaccine at 2, 4, and 12 months of age.
Congenital, familial and genetic disorders Hydrocele	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Gastrointestinal disorders Diarrhoea	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Gastrointestinal disorders Vomiting	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
General disorders Pyrexia	0.80% 2/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Abscess neck	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Adenovirus infection	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Bronchiolitis	0.80% 2/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	1.2% 3/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Bronchitis	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Gastroenteritis	0.00% 0/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.40% 1/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Gastroenteritis norovirus	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Parainfluenzae virus infection	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Perirectal abscess	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Pneumonia	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Pyelonephritis acute	0.00% 0/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.80% 2/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Respiratory syncytial virus bronchiolitis	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	1.2% 3/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Rhinovirus infection	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Infections and infestations Urinary tract infection	0.80% 2/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Investigations Enterovirus test positive	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Metabolism and nutrition disorders Hypophagia	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Nervous system disorders Febrile convulsion	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.40% 1/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Nervous system disorders Seizure	0.80% 2/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Reproductive system and breast disorders Testicular torsion	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.40% 1/249 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).	0.00% 0/251 • Serious Adverse Events (SAEs) were collected throughout the entire period of the study (from Day 1 up to study end [Month 11]). Non Serious AEs (Other AEs) were collected during the 31 days follow-up period after each vaccination (vaccines administered at 2,4 and 12 months of age).