A Phase III randomized, double-blind, clinical trial of an investigational hexavalent vaccine given at 2, 4, and 11-12 months

Vaccine. 2016 Jul 19;34(33):3810-6. doi: 10.1016/j.vaccine.2016.05.054. Epub 2016 Jun 18.

Abstract

Background: Combination vaccines simplify vaccination visits and improve coverage and timeliness. DTaP5-HB-IPV-Hib is a new investigational, fully-liquid, combination vaccine designed to protect against 6 infectious diseases, including 5 pertussis antigens and OMPC instead of PT as conjugated protein for Hib component.

Methods: In this multicenter, double-blind, comparator-controlled, Phase III study (NCT01480258) conducted in Sweden, Italy, and Finland, healthy infants were randomized 1:1 to receive one two immunization regimens. The DTaP5-HB-IPV-Hib Group received the investigational hexavalent vaccine (DTaP5-HB-IPV-Hib) and the Control Group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 4 and 11-12months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) or Rotarix (RV1) at 2, 4months of age and PCV13 at 11-12months. Subjects administered RV5 received a 3rd dose at 5months of age.

Results: A total of 656 subjects were randomized to the DTaP5-HB-IPV-Hib Group and 659 subjects to Control Group. Immune responses to all vaccine antigens post-toddler dose were non-inferior in the DTaP5-HB-IPV-Hib Group as compared to the Control Group. Additionally, the post-dose 2 and pre-toddler DTaP5-HB-IPV-Hib anti-PRP responses were superior. The DTaP5-HB-IPV-Hib Group responses to concomitant RV1 were non-inferior compared to the Control Group. Solicited adverse event rates after any dose were similar in both groups, except for higher rates of pyrexia (6.4% difference; 95% CI: 1.5,11.3) and somnolence (5.8% difference; 95% CI: 1.7,9.8) in the DTaP5-HB-IPV-Hib Group. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib Group (0.3%) and the Control Group (0.5%).

Conclusions: The safety and immunogenicity of DTaP5-HB-IPV-Hib is generally comparable to Control when administered in the 2, 4, 11-12month schedule. Early Hib responses were superior versus Control. DTaP5-HB-IPV-Hib could provide a new hexavalent option for pediatric combination vaccines, aligned with recommended immunizations in Europe.

Study identification: V419-008 CLINICALTRIALS.GOV identifier: NCT01480258.

Keywords: DTaP; Hepatitis B; Hexavalent; Hib; Immunogenicity; Polio; Safety; Vaccine.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibodies, Viral / blood
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage*
  • Diphtheria-Tetanus-Pertussis Vaccine / therapeutic use
  • Double-Blind Method
  • Female
  • Finland
  • Haemophilus Vaccines / administration & dosage*
  • Haemophilus Vaccines / therapeutic use
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / therapeutic use
  • Humans
  • Infant
  • Italy
  • Male
  • Pneumococcal Vaccines / administration & dosage
  • Poliovirus Vaccine, Inactivated / administration & dosage*
  • Poliovirus Vaccine, Inactivated / therapeutic use
  • Rotavirus Vaccines / administration & dosage
  • Sweden
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / therapeutic use

Substances

  • 13-valent pneumococcal vaccine
  • Antibodies, Bacterial
  • Antibodies, Viral
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Haemophilus Vaccines
  • Hepatitis B Vaccines
  • Pneumococcal Vaccines
  • Poliovirus Vaccine, Inactivated
  • RIX4414 vaccine
  • RotaTeq
  • Rotavirus Vaccines
  • Vaccines, Attenuated
  • Vaccines, Combined
  • diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine

Associated data

  • ClinicalTrials.gov/NCT01480258