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

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.

Time frame: 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.

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.

Time frame: 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 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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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\]). 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.

Time frame: From D1 to D15 after any vaccination

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

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.

Time frame: 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.