Safety, immune lot-to-lot consistency and non-inferiority of a fully liquid pentavalent DTwP-HepB-Hib vaccine: Results from Phase III licensure study of Shan5™

Abstract

Background: Pentavalent combination vaccines perform a key role in increasing vaccine coverage rate; and provide an efficient and reliable method of implementing WHO recommendations for controlling diphtheria, tetanus, pertussis, hepatitis B and Hib infections on a worldwide basis. Methods & Materials: Study design: A phase III, multi-center, randomized, single blinded study of a fully liquid pentavalent DTwP-HepB-Hib investigational vaccine (Shan5™) was conducted across India in healthy toddlers and infants. Cohort 1 consisted of 15 toddlers aged 15-18 months, administered with a single booster dose; Cohort 2 consisted of 1085 infants aged 6-8 weeks, administered 3 doses at 6-8, 10-12 and 14-16 weeks of age. Objectives: Subjects in Cohort 1 were evaluated for safety and immunogenicity. Immunogenicity and safety were evaluated in Cohort 2 subjects vaccinated with a three-dose primary immunization of either the investigational vaccine or a locally licensed comparator vaccine (Pentavac™ SD). Immune consistency analysis among three lots of the investigational vaccine, and immune non-inferiority analysis of pooled (three lots) data of investigational vaccine versus comparator vaccine were also evaluated in cohort 2. Results: The vaccines demonstrated comparable safety and immune responses in cohort 1. In cohort 2, immune non-inferiority against the comparator vaccine (primary endpoint) was demonstrated for all five antigens and safety results (secondary endpoint) were comparable between vaccine groups. Equivalent immune consistency among three lots was observed for all antigens except whole cell pertussis antigens, where a marginal variation was observed. The variation was linked to the low power of the test and concluded to be clinically insignificant. Conclusion: The investigational, fully-liquid, whole-cell pertussis (wP) containing pentavalent vaccine has a good safety profile and immunologically non-inferior to the licensed comparator vaccine. This study was the basis for licensure in India and also WHO- prequalification for international use.