Author information

• ¹Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
• ²Nephrology, KfH-Nierenzentrum Berlin-Neukölln, in Berlin-Neukölln, Germany.
• ³Kidney and Dialysis Center, MVZ DaVita Rhein Ruhr, Düsseldorf, Germany.
• ⁴Internal Medicine, MVZ Lütten Klein, Nephrocare Rostock GmbH, Rostock, Germany.
• ⁵Department of Nephrology and Kuratorium for Dialysis and Transplantation Renal Unit, Hospital St. Georg, Martin-Luther-University Halle/Wittenberg, Leipzig, Germany.
• ⁶Lipid Clinic, Nephrocare Hamburg-Barmbek, Hamburg, Germany.
• ⁷Internal Medicine, KfH, Nierenzentrum, Munich, Germany.
• ⁸Center of Nephrology, Mettmann, Germany.
• ⁹Nierenzentrum Mannheim, Mannheim-Käfertal, Germany.
• ¹⁰Internal Medicinem Regulatory and Medical Affairs, Nephrologische Gemeinschaftspraxis, Mainz, Germany.
• ¹¹Klinik für Nieren- und Hochdruckkrankheiten and Bereich Endokrinologie und Stoffwechselkrankheiten, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
• ¹²Department of Infectious Diseases, West German Centre of Infectious Diseases, Universitätsmedizin Essen, University Duisburg-Essen, Essen, Germany.
• ¹³Dynavax Technologies Corporation, Emeryville, California, USA.
• ¹⁴HBV-18 Study Investigators: Herman Haller, Medizinische Hochschule Hannover, Hannover, Germany; Clemens Grupp, Sozialstiftung Bamberg, Bamberg, Germany; Jens Passauer, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; Gert-Peter Dragoun, KfH Nierenzentrum, Aschaffenburg, Germany; Thomas Strack, KfH Nierenzentrum Munich-Schwabing, Munich, Germany; Tobias Marsen, KfH Nierenzentrum, Cologne, Germany; Stefan Weiner, Krankenhaus der Barmherzigen Brüder, Nordallee, Germany; Norbert Bockreiss, KfH Nierenzentrum, Oberschleissheim, Germany.

Abstract

This study compared the immunogenicity and safety of a booster dose of HepB-CpG (HEPLISAV-B® vaccine) with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in patients receiving chronic hemodialysis. This was a multicenter, randomized, open-label, phase 3 study of adults receiving hemodialysis with antibodies to HBsAg (anti-HBs) <10 mIU/mL at study entry. The objective was to compare the seroprotection rate (SPR) induced by HepB-CpG with HepB-Eng or HepB-AS04. The SPR was defined as the percentage of patients with anti-HBs ≥10 mIU/mL post-vaccination. At 20 sites in Germany, 155 participants were randomized: HepB-CpG = 54; HepB-Eng = 50; and HepB-AS04 = 51. Of the 149 participants in the modified intention-to-treat population, 76.5% had not previously responded to at least one series of hepatitis B vaccine. Based on a post hoc analysis, the SPR in HepB-CpG recipients (52.8%; 95% confidence interval [CI]: 38.6%, 66.7%) was significantly higher than in HepB-Eng recipients (32.6%; 95% CI: 19.5%, 48.0%), and non-inferior to that in HepB-AS04 recipients (43.1%; 95% CI: 29.3%, 57.8%). Local post-injection reactions occurred in significantly fewer HepB-CpG (9.3%) than HepB-AS04 recipients (31.4%; p = .007) and at a similar rate to HepB-Eng recipients (8.2%). Systemic post-injection reactions in HepB-CpG recipients (18.5%) were similar to the HepB-AS04 group (19.6%) and higher than in the HepB-Eng group (12.2%). In this difficult-to-immunize population, a booster dose of HepB-CpG induced significantly higher levels of seroprotection than HepB-Eng with a similar safety profile. The higher levels of immunogenicity were not accompanied by higher levels of local post-injection reactions compared with HepB-AS04.