Trial Outcomes & Findings for Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 11 to 12 Months (V419-008) (NCT NCT01480258)

Last Updated: 2019-04-02

Results Overview

Acceptability response rates were defined as Ab titre ≥1.0 μg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); ≥10 mIU/mL for Hepatitis (HBsAg); ≥0.1 IU/mL for diphtheria and tetanus; ≥8 (1/dil) for inactive poliovirus type (IPV) 1, 2 \& 3, and percentage of pertussis seroresponder participants (Pertussis toxoid \[PT\], Filamentous haemagglutinin \[FHA\], Fimbriae types 2 \& 3 \[FIM\] and Pertactin \[PRN\]) 1 month Post-Toddler dose of PR5I. Seroresponse was defined: (1) If pre-Dose 1 Ab concentration (cc) was \<LLOQ (lower limit of quantitation), postvaccination Ab cc was ≥LLOQ, (2) If pre-Dose 1 Ab cc was ≥LLOQ, postvaccination Ab cc was ≥prevaccination levels. Due to the timing of the occurrence of protocol violation or the availability of each antigen serology testing result, the analysis populations may not have been identical for each antigen-specific analysis at each post-vaccination visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1315 participants

Primary outcome timeframe

1 month after Toddler dose of PR51 (post-toddler dose)

Results posted on

2019-04-02

Participant Flow

Participants from Italy and Sweden were randomized to Rotavirus Vaccine Subset 1 (Rotarix™). Participants from Finland were randomized to Rotavirus Vaccine Subset 2 (RotaTeq™).

Participant milestones

Participant milestones
Measure	PR5I Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Infant Series STARTED	656	659
Infant Series Vaccinated	653	659
Infant Series COMPLETED	649	651
Infant Series NOT COMPLETED	7	8
Interim Period STARTED	649	651
Interim Period COMPLETED	639	642
Interim Period NOT COMPLETED	10	9
Toddler Dose STARTED	639	642
Toddler Dose COMPLETED	639	642
Toddler Dose NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	PR5I Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Infant Series Protocol Violation	2	0
Infant Series Physician Decision	0	1
Infant Series Not Vaccinated	3	0
Infant Series Adverse Event	1	1
Infant Series Withdrawal by Subject	1	6
Interim Period Lost to Follow-up	0	2
Interim Period Physician Decision	1	0
Interim Period Protocol Violation	0	1
Interim Period Withdrawal by Subject	9	6

Baseline Characteristics

Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 11 to 12 Months (V419-008)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PR5I n=656 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=659 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	Total n=1315 Participants Total of all reporting groups
Age, Continuous	68 Days STANDARD_DEVIATION 10.3 • n=5 Participants	68.1 Days STANDARD_DEVIATION 10.5 • n=7 Participants	68.1 Days STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	323 Participants n=5 Participants	313 Participants n=7 Participants	636 Participants n=5 Participants
Sex: Female, Male Male	333 Participants n=5 Participants	346 Participants n=7 Participants	679 Participants n=5 Participants
Region of Enrollment Finland	459 Participants n=5 Participants	460 Participants n=7 Participants	919 Participants n=5 Participants
Region of Enrollment Italy	132 Participants n=5 Participants	132 Participants n=7 Participants	264 Participants n=5 Participants
Region of Enrollment Sweden	65 Participants n=5 Participants	67 Participants n=7 Participants	132 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 month after Toddler dose of PR51 (post-toddler dose)

Population: Participants who met the inclusion criteria, were not protocol violators, received PR51 vaccinations within acceptable day ranges, and had a blood draw sample window of Days 28 to 51 following the Toddler dose. Participants receiving INFANRIX™ hexa were excluded from the acceptability analyses.

Outcome measures

Outcome measures
Measure	PR5I n=638 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-PRP ≥1.0 μg/mL	89.87 Percentage of participants Interval 86.72 to 92.49	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-HBsAg ≥10 mIU/mL	98.14 Percentage of participants Interval 96.21 to 99.25	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-Diphtheria ≥0.1 IU/mL	98.64 Percentage of participants Interval 97.35 to 99.41	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-Tetanus ≥0.1 IU/mL	99.83 Percentage of participants Interval 99.06 to 100.0	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-PT seroresponse	99.12 Percentage of participants Interval 97.95 to 99.71	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-FHA seroresponse	97.42 Percentage of participants Interval 95.78 to 98.55	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-FIM seroresponse	98.28 Percentage of participants Interval 96.86 to 99.17	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-PRN seroresponse	96.91 Percentage of participants Interval 95.16 to 98.16	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-IPV1 ≥1:8 dilution	99.32 Percentage of participants Interval 98.28 to 99.82	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-IPV2 ≥1:8 dilution	99.83 Percentage of participants Interval 99.06 to 100.0	—
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) Anti-IPV3 ≥1:8 dilution	99.49 Percentage of participants Interval 98.52 to 99.9	—

SECONDARY outcome

Timeframe: 1 month after the 2nd dose (post-infant dose 2)

Population: Participants who received 2nd dose in the Infant series and had a blood draw sample window of Days 28 to 51 post-infant dose 2.

Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by radioimmunoassay (RIA) 1 month post-infant dose 2 of PR5I or INFANRIX hexa.

Outcome measures

Outcome measures
Measure	PR5I n=609 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=592 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Non-inferiority of Antibody (Ab) Response Rate to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa	72.86 Percentage of participants	26.66 Percentage of participants

SECONDARY outcome

Timeframe: 1 month after the 2nd dose (post-infant dose 2)

Population: Participants who received 2nd dose in the Infant series and had a blood draw sample window of Days 28 to 51 post-infant dose 2.

Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by RIA 1 month post-infant dose 2 of PR5I or INFANRIX hexa.

Outcome measures

Outcome measures
Measure	PR5I n=609 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=592 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Superiority of Antibody (Ab) Response Rates to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa	72.86 Percentage of participants	26.66 Percentage of participants

SECONDARY outcome

Timeframe: 1 month after Toddler dose (post-toddler dose)

Population: Participants who met the inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and had a blood draw sample window of Days 28 to 51 following the Toddler dose.

Percentage of participants with pre-specified Ab titre for PRP, HBsAg, diphtheria, tetanus, IPV1, 2 \& 3, and percentage of pertussis seroresponder participants (PT, FHA, FIM and PRN) 1 month post-toddler dose were calculated based on the method by Miettinen and Nurminen stratified by country. Seroresponse was defined: (1) If pre-Dose 1 Ab cc was \<LLOQ, post-vaccination Ab cc was ≥LLOQ, (2) If pre-Dose 1 Ab cc was ≥LLOQ, post-vaccination Ab cc was ≥pre-vaccination levels. Due to the timing of the occurrence of protocol violation or the availability of each antigen serology testing result, the analysis populations may not have been identical for each antigen-specific analysis at each post-vaccination visit.

Outcome measures

Outcome measures
Measure	PR5I n=638 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=642 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-IPV3 ≥1:8 dilution	99.49 Percentage of participants	99.65 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-Diphtheria ≥0.1 IU/mL	98.62 Percentage of participants	99.83 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-PRP ≥1.0 μg/mL	89.80 Percentage of participants	91.06 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-HBsAg ≥10 mIU/mL	98.14 Percentage of participants	98.73 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-Tetanus ≥0.1 IU/mL	99.83 Percentage of participants	100.00 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-PT seroresponse	99.11 Percentage of participants	99.64 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-FHA seroresponse	97.40 Percentage of participants	99.13 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-PRN seroresponse	96.86 Percentage of participants	98.28 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-IPV1 ≥1:8 dilution	99.32 Percentage of participants	99.83 Percentage of participants
Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa Anti-IPV2 ≥1:8 dilution	99.83 Percentage of participants	100.00 Percentage of participants

SECONDARY outcome

Timeframe: 1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2)

Population: Participants who received dose 2 of Rotarix.

Antibody titres expressed in units/mL were measured for Rotavirus IgA by Enzyme Immunoassay (EIA), 1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2). The 95% CI for GMT was based on the t-distribution of the natural log-transformed antibody titer.

Outcome measures

Outcome measures
Measure	PR5I n=160 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=171 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Non-inferiority of Rotavirus Response (Geometric Mean Titer, GMT) One Month After the 2nd Dose of Rotarix (4 Months of Age) Administered Concomitantly With PR5I Versus INFANRIX Hexa	96.41 Titre (units/mL) Interval 71.69 to 129.65	122.24 Titre (units/mL) Interval 92.48 to 161.58

SECONDARY outcome

Timeframe: Solicited AEs: up to 5 days (Days 1-5 after any vaccination); unsolicited AEs: up to 15 days (Day 1-15 after any vaccination)

Population: All randomized participants who received at least 1 vaccination and who had safety follow-up.

Injection-site and systemic AEs were reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 (D1) to D15 after each vaccination. Solicited injection site and systemic AEs were reported daily from D1 to D5 after each vaccination. AEs at injection sites were always considered as vaccine-related (V-related) (Injection-Site Reactions \[ISRs\]). The investigator had to assess whether systemic AEs were related or not to the vaccine. All AEs (related and unrelated) are displayed here.

Outcome measures

Outcome measures
Measure	PR5I n=653 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=659 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 V-related systemic AE (D1-D15)	99.1 Percentage of participants	98.3 Percentage of participants
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 ISR or systemic AE (D1-D15)	99.5 Percentage of participants	99.2 Percentage of participants
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 ISR or V-related systemic AE (D1-D15)	99.5 Percentage of participants	98.8 Percentage of participants
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 ISR (D1-D15)	90.8 Percentage of participants	88.2 Percentage of participants
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 solicited ISR (D1-D5)	90.4 Percentage of participants	87.9 Percentage of participants
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 systemic AE (D1-D15)	99.1 Percentage of participants	98.9 Percentage of participants
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 solicited systemic AE (D1-D5)	99.1 Percentage of participants	98.3 Percentage of participants
Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination At least 1 V-related solicited systemic AE (D1-D5)	99.1 Percentage of participants	98.2 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 days (Day 1 to Day 5 following vaccination)

Population: All randomised participants who received at least 1 vaccination and who had safety follow-up.

Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions \[ISRs\]). Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from D1 to D5 after vaccination.

Outcome measures

Outcome measures
Measure	PR5I n=653 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=659 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Percentage of Participants Reporting Solicited ISRs From D1 to D5 After Any Vaccination Injection-site erythema	68.6 Percentage of participants	60.4 Percentage of participants
Percentage of Participants Reporting Solicited ISRs From D1 to D5 After Any Vaccination Injection-site pain	73.4 Percentage of participants	70.0 Percentage of participants
Percentage of Participants Reporting Solicited ISRs From D1 to D5 After Any Vaccination Injection-site swelling	56.8 Percentage of participants	49.3 Percentage of participants

SECONDARY outcome

Timeframe: From D1 to D15 after any vaccination

Population: All randomised participants who received at least 1 vaccination and who had safety follow-up.

Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions {ISRs\]). Unsolicited ISRs occurring from Day 1 (D1) to D15 after any vaccination were reported daily on the VRC by the parent(s) or legal representative. Unsolicited ISRs with incidence ≥1% are reported below.

Outcome measures

Outcome measures
Measure	PR5I n=653 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=659 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination Injection-site haemorrhage	1.8 Percentage of participants	1.8 Percentage of participants
Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination Injection-site bruising	0.9 Percentage of participants	2.0 Percentage of participants
Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination Injection-site induration	15.8 Percentage of participants	13.2 Percentage of participants
Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination Injection-site nodule	1.1 Percentage of participants	0.8 Percentage of participants
Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination Injection-site warmth	2.3 Percentage of participants	1.2 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5 days (from D1 to D5 after any vaccination)

Population: All randomised participants who received at least 1 vaccination and who had safety follow-up.

Solicited systemic AEs were defined as crying, decreased appetite, irritability, pyrexia (rectal temperature ≥38.0°C), somnolence, and vomiting occurring from D1 to D5 after vaccination. The investigator had to assess whether these systemic AEs were related or not to the vaccines. All (related and unrelated) are displayed here.

Outcome measures

Outcome measures
Measure	PR5I n=653 Participants Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=659 Participants Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination Decreased appetite	65.8 Percentage of participants	62.2 Percentage of participants
Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination Crying	89.3 Percentage of participants	87.1 Percentage of participants
Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination Irritability	91.6 Percentage of participants	89.4 Percentage of participants
Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination Pyrexia	73.8 Percentage of participants	67.4 Percentage of participants
Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination Somnolence	86.1 Percentage of participants	80.3 Percentage of participants
Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination Vomiting	32.8 Percentage of participants	31.0 Percentage of participants

Adverse Events

PR5I

Serious events: 6 serious events

Other events: 650 other events

Deaths: 0 deaths

INFANRIX™ Hexa

Serious events: 10 serious events

Other events: 653 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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 The Sponsor and Sponsor representative must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor or Sponsor representative as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	PR5I n=653 participants at risk Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=659 participants at risk Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	0.15% 1/653 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.00% 0/659 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Congenital, familial and genetic disorders Heart disease congenital	0.15% 1/653 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.00% 0/659 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Congenital, familial and genetic disorders Vitello-intestinal duct remnant	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Pyrexia	0.15% 1/653 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Gastroenteritis	0.15% 1/653 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.00% 0/659 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Injection site abscess	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Pneumonia respiratory syncytial viral	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Pyelonephritis	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Pyelonephritis acute	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Respiratory syncytial virus bronchiolitis	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Streptococcal infection	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Upper respiratory tract infection	0.15% 1/653 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 2 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Viral upper respiratory tract infection	0.15% 1/653 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.00% 0/659 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Nervous system disorders Convulsion	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.15% 1/653 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.00% 0/659 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Vascular disorders Kawasaki's disease	0.00% 0/653 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	0.15% 1/659 • Number of events 1 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.

Measure	PR5I n=653 participants at risk Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	INFANRIX™ Hexa n=659 participants at risk Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
Gastrointestinal disorders Abdominal pain	3.1% 20/653 • Number of events 23 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	1.5% 10/659 • Number of events 11 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Gastrointestinal disorders Constipation	3.4% 22/653 • Number of events 25 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	2.4% 16/659 • Number of events 18 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Gastrointestinal disorders Diarrhoea	11.6% 76/653 • Number of events 95 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	10.6% 70/659 • Number of events 84 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Gastrointestinal disorders Flatulence	4.4% 29/653 • Number of events 32 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	3.8% 25/659 • Number of events 29 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Gastrointestinal disorders Vomiting	33.7% 220/653 • Number of events 324 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	32.0% 211/659 • Number of events 319 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Crying	89.3% 583/653 • Number of events 1422 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	87.1% 574/659 • Number of events 1305 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Injection site bruising	2.0% 13/653 • Number of events 15 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	3.5% 23/659 • Number of events 24 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Injection site erythema	74.3% 485/653 • Number of events 1625 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	68.3% 450/659 • Number of events 1490 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Injection site haemorrhage	2.6% 17/653 • Number of events 21 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	2.6% 17/659 • Number of events 20 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Injection site induration	18.2% 119/653 • Number of events 266 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	16.2% 107/659 • Number of events 246 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Injection site pain	76.0% 496/653 • Number of events 1778 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	74.8% 493/659 • Number of events 1656 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Injection site swelling	62.2% 406/653 • Number of events 1179 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	56.6% 373/659 • Number of events 1083 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Irritability	91.6% 598/653 • Number of events 1518 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	89.4% 589/659 • Number of events 1446 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
General disorders Pyrexia	75.0% 490/653 • Number of events 875 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	68.6% 452/659 • Number of events 768 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Nasopharyngitis	5.4% 35/653 • Number of events 39 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	5.5% 36/659 • Number of events 39 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Otitis media	3.7% 24/653 • Number of events 26 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	2.3% 15/659 • Number of events 15 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Rhinitis	5.2% 34/653 • Number of events 39 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	6.2% 41/659 • Number of events 44 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Infections and infestations Upper respiratory tract infection	6.3% 41/653 • Number of events 45 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	6.5% 43/659 • Number of events 48 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Metabolism and nutrition disorders Decreased appetite	66.0% 431/653 • Number of events 731 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	62.4% 411/659 • Number of events 694 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Nervous system disorders Somnolence	86.1% 562/653 • Number of events 1168 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	80.3% 529/659 • Number of events 1118 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.
Respiratory, thoracic and mediastinal disorders Cough	4.6% 30/653 • Number of events 31 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.	3.6% 24/659 • Number of events 29 • Up to approximately 11 months (serious AEs and deaths were collected for the duration of the study; unsolicited adverse events were collected from D1 to D15 after each hexavalent vaccination, solicited adverse events were collected D1 to D5 after each hexavalent vaccination) Analysis population includes all randomised participants who received at least 1 vaccination and had safety follow-up.