A Phase III Randomized, Double-blind, Clinical Trial of an Investigational Hexavalent Vaccine Given at Two, Three, Four and Twelve Months

Background: Combination vaccines simplify vaccination visits and improve coverage and timeliness. Diphtheria-tetanus toxoids-acellular pertussis 5, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b ( DTaP5-HB-IPV-Hib) is a new investigational, fully liquid, combination vaccine containing a 5-antigen pertussis component and is designed to protect against 6 infectious diseases. Methods: In this multicenter, double-blind, comparator-controlled, phase III study (NCT01341639) conducted in Finland, Germany and Belgium, healthy infants were randomized 1: 1 to receive 1 of 2 immunization -regimens. The DTaP5-HB-IPV-Hib group received the investigational hexavalent vaccine (DTaP-HB-IPV-Hib) and the Control group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 3, 4 and 12 months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) at 2, 3 and 4 months of age and ProqQad (MMRV) at 12 months of age. MMRV was also administered to all study subjects at 13 months of age. Results: A total of 628 subjects in the DTaP5-HB-IPV-Hib group and 622 subjects in the Control group were randomized. In a per-protocol analysis, immune responses to vaccine antigens 1 month after dose 3 and after the toddler dose were noninferior in the DTaP5-HB-IPV-Hib group as compared with the Control group. The DTaP5-HB-IPV-Hib group responses to MMRV given concomitantly at 12 months were all noninferior compared with the Control group. Solicited adverse event rates after any dose, -including fever, were similar in both groups. Most adverse events were mild-to-moderate and did not lead to subject withdrawal. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib group (0.3%) and the Control group (0.2%). Conclusions: The safety and immunogenicity of DTaP5-HB-IPV-Hib is comparable to Control when administered in the 2-month, 3-month, 4-month and 12-month schedule. DTaP5-HB-IPV-Hib has the potential to provide a new hexavalent option for pediatric combination vaccines, aligned with recommended immunizations in Europe.