• Sam Jackson, Joseph Lentino, James Kopp, Linda Murray, William Ellison, Margaret Rhee, Gerald Shockey, Lalith Akella, Kimberly Erby, William L Heyward, Robert S Janssen, and HBV-23 Study Group.
• Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: sjackson@alkahest.com.
• Vaccine. 2018 Jan 29; 36 (5): 668-674.

BackgroundHepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke.MethodsPhase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status.ResultsAmong 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group.ConclusionTwo doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

30 keywords...

hide…