Background

This Phase 3 study evaluated the safety and immunogenicity of VAXNEUVANCE compared with PCV13 administered as a 2+1 dosing regimen in healthy and pre-term infants. This was administered concomitantly with other paediatric vaccines including diphtheria, tetanus and pertussis (DTaP)/inactivated poliovirus (IPV)/Haemophilus influenzae type B (Hib)/hepatitis B (HepB) and rotavirus vaccines.

Methods

• PNEU-PED-EU-1 was a Phase 3, multicentre, randomised, double-blind, active comparator-controlled study to evaluate the safety, tolerability and immunogenicity of a three-dose regimen of VAXNEUVANCE in healthy infants
• Healthy infants were randomised in a 1:1 ratio to receive either VAXNEUVANCE or PCV13 administered as a two-dose primary series at 2 and 4 months of age, followed by a toddler dose at 11–15 months of age
• Healthy preterm (<37 weeks) infants received a 3 + 1 dose schedule (three-dose primary series followed by a toddler dose) of PCV at approximately 2, 3, 4, and 11–15 months of age

Primary objectives

Safety and tolerability: To evaluate the safety and tolerability of VAXNEUVANCE with respect to the proportion of participants with adverse events (AEs).

Immunogenicity: To compare the anti-pneumococcal polysaccharide (PnPs) serotype-specific IgG response rates (proportion of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/ml), as well as immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days post-toddler dose (PTD) (post-dose 3 for full-term infants; post-dose 4 for pre-term infants) for participants administered VAXNEUVANCE versus PCV13.

Secondary objectives

• To compare the antigen-specific response rates to each antigen included in the DTaP/IPV/Hib/HepB vaccine 30 days PTD for participants administered VAXNEUVANCE versus PCV13
• To compare anti-rotavirus immunoglobulin A (IgA) geometric mean titres (GMTs) at 30 days post-primary series (PPS) for participants administered the rotavirus vaccine concomitantly with VAXNEUVANCE versus PCV13
• To evaluate the anti-PnPs serotype-specific opsonophagocytic activity (OPA) GMTs and response rates at 30 days PTD by each vaccination group

Results

• Of 1188 eligible participants who were randomised, 1184 were included in the final analysis:
  • In the VAXNEUVANCE group (N=591), 588 participants were vaccinated with at least one dose of VAXNEUVANCE
  • In the PCV13 group (N=593), 591 participants were vaccinated with at least one dose of PCV13
  • Reasons for discontinuation included protocol deviation, withdrawal, physician decision and loss to follow-up
• Across the VAXNEUVANCE and PCV13 groups, demographic and baseline characteristics were generally comparable
• Approximately 6% of participants were pre-term infants

Safety

• The proportions of participants with AEs, including injection-site, systemic and vaccine-related AEs, and serious adverse events (SAEs) were generally comparable between vaccination groups
  • No deaths were reported in either group
• The proportions of participants with solicited injection-site AEs and systemic AEs were generally comparable across both vaccination groups
  • Higher proportions of participants in the VAXNEUVANCE group compared with the PCV13 group were observed with solicited AEs of injection-site pain and irritability
  • Of the participants in the VAXNEUVANCE group with solicited AEs, the majority had events with a maximum intensity of mild or moderate and were of short duration (≤3 days)

• The most frequently reported AEs following vaccination with VAXNEUVANCE were irritability, somnolence and injection-site erythema
  • No vaccine-related SAEs were reported in participants receiving VAXNEUVANCE
• The majority of participants in the VAXNEUVANCE group reported body temperature measurements <38.5°C and, overall, temperature distribution was comparable to PCV13 and consistent with the overall study population
  • The numbers of participants with a maximum temperature ≥39°C were 18.9% and 14.6% in the VAXNEUVANCE and PCV13 groups, respectively; however, the majority of these were below 40.5°C
• VAXNEUVANCE was well tolerated in pre-term participants, with a safety profile comparable to PCV13 and consistent with the overall study population (including full-term and pre-term infants)

Immunogenicity results

• VAXNEUVANCE met non-inferiority criteria for the 13 shared serotypes, as assessed by the proportions of participants meeting the threshold value of ≥0.35 μg/ml (response rate) for each serotype and serotype-specific IgG GMCs at 30 days PTD
• VAXNEUVANCE met superiority criteria for the two additional serotypes (22F and 33F), as assessed by response rates and serotype-specific IgG GMCs at 30 days PTD

Conclusions

In healthy infants ~2 months of age:

• VAXNEUVANCE is well tolerated, with a safety profile generally comparable to PCV13
• VAXNEUVANCE is non-inferior to PCV13 for the 13 shared serotypes and superior to PCV13 for the two additional serotypes (22F and 33F) at 30 days PTD, as assessed by serotype-specific IgG responses (response rates and GMCs)
• VAXNEUVANCE induces functional antibodies (OPA) capable of bactericidal killing of Streptococcus pneumoniae PPS and PTD
• VAXNEUVANCE can be administered concomitantly with licensed paediatric vaccines (DTaP/IPV/Hib/HepB and rotavirus)