Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 Randomized Clinical Trial in the Russian Federation

Elena V Esaulenko, Aleksey A Yakovlev, Genady A Volkov, Anastasia A Sukhoruk, Kirill G Surkov, Peter V Kruglyakov, Francisco Diaz-Mitoma, Elena V Esaulenko, Aleksey A Yakovlev, Genady A Volkov, Anastasia A Sukhoruk, Kirill G Surkov, Peter V Kruglyakov, Francisco Diaz-Mitoma

Abstract

Background: This study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia.

Methods: We conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18-45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: > - 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC).

Results: Rate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: -2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was >97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported.

Conclusions: 3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.

Keywords: hepatitis B; seroconversion; seroprotection; vaccine.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials flowchart depicting the study events. Abbreviations: 1AV, single antigen vaccine; 3AV, 3-antigen vaccine.
Figure 2.
Figure 2.
Time course of anti-HBs titers (mIU/mL). Concentrations of antibodies induced by 3AV were significantly higher than those induced by 1AV at days 90 (P = .001) and 180 (P = .0001). Abbreviations: 1AV, single antigen vaccine; 3AV, 3-antigen vaccine; HBs, hepatitis B surface.
Figure 3.
Figure 3.
Frequency of local reactions (erythema, itching, pain) in both study arms for each injection administered. Frequency of local reactions due to 3AV and 1AV, assessed using the 1-sided variant of z-criterion, was similar throughout the study. Abbreviations: 1AV, single antigen vaccine; 3AV, 3-antigen vaccine.

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Source: PubMed

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