A single blind randomized phase 3 study to evaluate safety and immunogenicity of inactivated hepatitis A vaccine (HAPIBEVTM) in 1-15 years-old healthy hepatitis A vaccine-naïve children.

The Biological E inactivated hepatitis A (HAPIBEV™) vaccine was developed by importing the Healive® vaccine bulk from China and fill-finish it in India. Healive® vaccine is approved in China for both children and adults. This study assessed the safety and immunogenicity of HAPIBEV™ vaccine as compared to the Havrix 720® vaccine of GlaxoSmithKline (GSK) pharmaceuticals when administered intramuscularly (IM) 6 months apart in 1-15 years old hepatitis A virus (HAV) vaccine naive children in India. This Phase 3, single blind, parallel, randomized, active-controlled, two-arm study was conducted at 8 centers in India in healthy HAV vaccine-naive children. Subjects were stratified into 2 age subsets (1-7 and 8-15 years) and randomly assigned to either BE-HAPIBEV™ or GSK's Havrix® vaccine and administered 2 IM injections 6 months apart. The immunogenicity evaluations included: (1) proportion of subjects who achieved the following at Day 210 from baseline: (a) seroconversion (≥20 mIU/mL) with anti-HAV immunoglobulin G (IgG) antibodies, (b) ≥4-fold increase in anti-HAV IgG antibodies, and (c) ≥2-fold increase in anti-HAV IgG antibodies concentration who were already seroconverted at baseline and (2) geometric mean concentrations (GMC) of anti-HAV IgG antibodies at baseline and Day 210. Safety was evaluated throughout the study. A total of 467 (89.8%) subjects completed the study. The non-inferiority criterion was met by HAPIBEV™ vaccine as seroconversion rates in both vaccine groups were 100%. Overall, other immunogenicity evaluations were either similar in both vaccine groups or higher in the HAPIBEV™ group compared with the Havrix® group. The safety profile was also comparable between HAPIBEV™ and Havrix® groups. The most common adverse event (AE) was injection site pain, and the majority of AEs were mild in severity. The HAPIBEV™ vaccine demonstrated an immunological and safety profile on par with Havrix® in 1-15 years old healthy HAV vaccine-naive Indian children. This study is registered with clinical trial registry of India bearing no: CTRI/2019/04/018384 on 02 Apr 2019.