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.

BACKGROUND This study compares the immunogenicity and safety of a 3-antigen (S/preS1/preS2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. METHODS Randomized, double-blind, comparative study of three-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% 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 non-inferior 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 = 0.001) and 180 (p = 0.0001) with 3AV. Sex, age, and 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 = 0.15), second (20.0% vs 14.6%, p = 0.33) and third vaccination (14.9% vs 23.4%, p = 0.22). No SAEs were reported. CONCLUSIONS 3AV was non-inferior to 1AV. 3AV induced high SPR and there were no safety concerns.