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



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.



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%).



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.



V419-008 CLINICALTRIALS.GOV identifier: NCT01480258.
Umeå University, Umeå, Sweden.
Sven-Arne
SA
Silfverdal
University of Genoa, IRCCS AOU San Martino, Genoa, Italy.
Giancarlo
G
Icardi
University of Tampere, Tampere, Finland.
Timo
T
Vesikari
Merck & Co., Inc., Kenilworth, NJ, United States.
Sheryl A
SA
Flores
Merck & Co., Inc., Kenilworth, NJ, United States.
Marco F
MF
Pagnoni
Merck & Co., Inc., Kenilworth, NJ, United States.
Jin
J
Xu
Merck & Co., Inc., Kenilworth, NJ, United States.
G Frank
GF
Liu
Merck & Co., Inc., Kenilworth, NJ, United States.
Jon E
JE
Stek
Sanofi Pasteur MSD, Lyon, France.
Florence
F
Boisnard
Sanofi Pasteur MSD, Lyon, France.
Stéphane
S
Thomas
Sanofi Pasteur MSD, Lyon, France.
Eddy
E
Ziani
Merck & Co., Inc., Kenilworth, NJ, United States. Electronic address: andrew_wen-tseng_lee@merck.com.
Andrew W
AW
Lee
D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005387:Finland; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D022242:Pneumococcal Vaccines / Q000008:administration & dosage; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage* / Q000627:therapeutic use; D022243:Rotavirus Vaccines / Q000008:administration & dosage; D013548:Sweden; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000627:therapeutic use
C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D022242:Pneumococcal Vaccines; D011054:Poliovirus Vaccine, Inactivated; C492457:RIX4414 vaccine; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated; D017778:Vaccines, Combined; C541235:diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine
DTaP; Hepatitis B; Hexavalent; Hib; Immunogenicity; Polio; Safety; Vaccine