Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Issue 5 (29th January 2018)

• Record Type: Journal Article
• Authors: Adams, Michael; Bolshoun, David; Bruce, Tami; Chuang, Rita; DeSantis, Donna; Fiel, Thomas; Fitzgibbons, William; Francyk, David; Geisberg, Harry; Giep, Son; Godbole, Narendra; Haas, Terry; Halpern, Stephen; Inzerello, Anthony; Jennings, William; Kaiser, Scott; Kay, Jennifer; Kirby, William; Lending, Robert; Levins, Peter; Molin, Clifford; Noss, Michael; Kotek, Larry; Reynolds, Michele; Riffer, Ernie; Schumacher, Douglas; Severance, Randall; Solano, Royce; Tejada, Albert; Tharenos, Leslie; Throne, Martin; Turner, Merle; Wolf, Thomas; Woodruff, Mark; Jackson, Sam; Lentino, Joseph; Kopp, James; Murray, Linda; Ellison, William; Rhee, Margaret; Shockey, Gerald; Akella, Lalith; Erby, Kimberly; Heyward, William L.; Janssen, Robert S.;
• Is Part Of: Vaccine. Volume 36:Issue 5(2018)
• Page Start: 668
• Page End: 674
• Publication Date: 2018-01-29
• Subjects: Hepatitis B vaccine -- Toll-like receptor 9 -- HEPLISAV-B -- Engerix-B -- Diabetes mellitus; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.12.038
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Phase 3 trial of an investigational 2 dose hepatitis B vaccine in diabetes mellitus. 2 doses of HBsAg-1018 induced significantly higher seroprotection rates than HBsAg-Eng. HBsAg-1018 demonstrated better consistency of SPRs in subpopulations than HBsAg-Eng. Abstract: Background: Hepatitis 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. Methods: Phase 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. Results: Among 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. Conclusion: Two 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 Registrationclinicaltrials.gov Identifier: NCT02117934.