Integrated Safety Profile of a New Approved, Fully Liquid DTaP5-HB-IPV-Hib Vaccine.

BACKGROUND: DTaP5-HB-IPV-Hib is a fully liquid, hexavalent vaccine containing a 5-antigen pertussis component, approved since 2016 in Europe [Vaxelis; DTaP5-HB-IPV-Hib vaccine: Diphtheria, tetanus, pertussis (5 acellular components: pertussis toxoid [PT], filamentous haemagglutinin [FHA], pertactin (PRN), and fimbriae Types 2 and 3 [FIM]), hepatitis B (recombinant DNA: rDNA), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed); MCM Vaccine B.V., The Netherlands] for primary and booster vaccination in infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b. The comparator vaccine (control) was INFANRIX hexa (GlaxoSmithKline Biologics S.A., Rixensart, Belgium) (DTaP3-IPV-HepB/Hib) in European studies and PENTACEL (DTaP5-IPV/Hib) (Sanofi Pasteur, Swiftwater, PA) in US studies. METHODS: Data from 6 studies were integrated and analyzed to provide a comprehensive safety profile. Numbers and proportions of subjects with adverse events (AEs) were summarized by treatment group. Group differences in proportion of AEs were calculated. RESULTS: Among the DTaP5-HB-IPV-Hib (N = 5223) and 2295 control (N = 2295) groups, solicited injection-site and systemic AEs were very common. Serious AEs were reported by 3.9% of DTaP5-HB-IPV-Hib and 3.7% of control subjects. Vaccine-related serious AEs occurred infrequently, 0.2% for both groups. Most AEs were mild-to-moderate and did not lead to subject withdrawal. Group differences for solicited systemic AEs were small (<3%) and not statistically significant, except for pyrexia (estimated difference 9.4% [95% CI: 6.7%-12%]). The difference was driven by the 2 US studies where the PENTACEL control group had a lower fever rate. Among European studies, there was no significant difference in rates of pyrexia between DTaP5-HB-IPV-Hib and INFANRIX hexa. CONCLUSIONS: The safety of DTaP5-HB-IPV-Hib is consistent with the safety profile of its components and similar to comparator vaccines, including INFANRIX hexa. The vaccine provides a new, fully liquid and convenient hexavalent vaccination option for use with various vaccination schedules in Europe.

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.

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

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.

What are the preferences of health care professionals in Germany regarding fully liquid, ready-to-use hexavalent pediatric vaccine versus hexavalent pediatric vaccine that needs reconstitution?

Diphtheria, tetanus and acellular pertussis (DTaP) based combined vaccines have led to significant reduction in incidence of several serious pediatric infectious diseases. A new, fully liquid combined hexavalent vaccine has been introduced and has been shown to reduce administration time. This fully liquid vaccine may also be simpler to administer and could reduce handling errors. The present study was designed to understand the value that health care providers (HCPs) place on aspects of injection devices for combined hexavalent vaccine programs in Germany. A discrete choice experiment (DCE) was designed to elicit the views of HCPs regarding hexavalent vaccines. The key attributes of injection devices were identified through a focused literature search and interviews with HCPs. Five key attributes, each with two or three levels were described which included: type of device, experience of this hexavalent vaccine on the German market, preparation time, probability of handling errors, and dosage errors. Physicians (n=150) and nurses (n=150) who administered hexavalent vaccines in Germany completed the survey. Choice data were analyzed using the conditional logit procedure. All attributes were significant and important independent influences on physicians' and nurses' choices. Reducing any "probability of dosage errors" was the most important attribute. Both physicians and nurses had a strong preference to reduce preparation time. All other things equal both groups also significantly preferred a fully liquid hexavalent vaccine. They also preferred vaccines that had been on the market for a few years compared to ones that had not (especially the physicians). Additional analyses explored participants' preferences in more detail through interaction terms. The DCE choice data provide useful insights into how HCPs view each aspect of the vaccination device. Overall, the HCPs preferred fully liquid vaccines. The survey also highlighted the importance of handling and dosage errors, reducing preparation time, and also experience of the HCPs with the use of a vaccine. The survey work included physicians and nurses and explored their views separately.

Assessment of preparation time with fully-liquid versus non-fully liquid paediatric hexavalent vaccines. A time and motion study.

BACKGROUND AND AIMS: Simplified vaccine preparation steps would save time and reduce potential immunisation errors. The aim of the study was to assess vaccine preparation time with fully-liquid hexavalent vaccine (DTaP-IPV-HB-PRP-T, Sanofi Pasteur MSD) versus non-fully liquid hexavalent vaccine that needs reconstitution (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals). METHODS: Ninety-six Health Care Professionals (HCPs) participated in a randomised, cross-over, open-label, time and motion study in Belgium (2014). HCPs prepared each vaccine in a cross-over manner with a wash-out period of 3-5min. An independent nurse assessed preparation time and immunisation errors by systematic review of the videos. HCPs satisfaction and preference were evaluated by a self-administered questionnaire. RESULTS: Average preparation time was 36s for the fully-liquid vaccine and 70.5s for the non-fully liquid vaccine. The time saved using the fully-liquid vaccine was 34.5s (p≤0.001). On 192 preparations, 57 immunisation errors occurred: 47 in the non-fully liquid vaccine group (including one missing reconstitution of Hib component), 10 in the fully-liquid vaccine group. 71.9% of HCPs were very or somewhat satisfied with the ease of handling of both vaccines; 66.7% and 67.7% were very or somewhat satisfied with speed of preparation in the fully-liquid vaccine and the non-fully liquid vaccine groups, respectively. Almost all HCPs (97.6%) stated they would prefer the use of the fully-liquid vaccine in their daily practice. CONCLUSIONS: Preparation of a fully-liquid hexavalent vaccine can be completed in half the time necessary to prepare a non-fully liquid vaccine. The simplicity of the fully-liquid hexavalent vaccine preparation helps optimise reduction of immunisation errors.