Immunogenicity and Safety of a Newly Developed Live Attenuated Varicella Vaccine in Healthy Children: A Multi-National, Randomized, Double-Blinded, Active-Controlled, Phase 3 Study

Abstract

Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 in healthy children to those of Varivax^TM (control). Children aged 12 months to 12 years were randomized in a ratio of 1:1 to receive either NBP608 or the control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. In total, 499 participants (NBP608, n = 251; control, n = 248) were enrolled. The seroconversion rate (SCR) measured using a FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for the SCR difference (NBP608 minus the control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of -15%. In an assessment using gpELISA, the SCR was 99.53% in the NBP608 group, and the 95% LCL for the SCR difference was 6.5%, which was higher than the specified non-inferiority margin of -15%. There were no significant differences between the NBP608 and control group with respect to the proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to Varivax^TM.

Keywords: children; clinical trial; immunogenicity; safety; vaccine; varicella.

Figure 1

Flow diagram for selection of study participants. The number in parenthesis ( ) is the number of participants in corresponding disposition. Abbreviation: PP, per-protocol.

Figure 2

The pre- and post-vaccination geometric mean titers (GMT) for both the NBP608 and control groups. These were assessed using two different methods, (A) a fluorescent-antibody-to-membrane-antigen (FAMA) assay, where the post-vaccination GMT was found to be higher in the NBP608 group compared to that in the control group (* p < 0.001), and (B) a glycoprotein enzyme-linked immunosorbent assay (gpELISA), where similarly, the post-vaccination GMT was higher in the NBP608 group than that in the control group (* p < 0.001). The results include data from baseline seropositive participants.