title: Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B.
abstract: GS-4774 is a heat-inactivated, yeast-based, T-cell vaccine designed to elicit hepatitis B virus (HBV)-specific T-cell responses. We evaluated the safety, tolerability and efficacy of GS-4774 in patients with chronic HBV infection.
  
  
  
  In this phase II study, 178 patients with chronic HBV infection and no cirrhosis who were virally suppressed on an oral antiviral (OAV) for ⩾1year were randomized (1:2:2:2) to continue OAV alone or receive OAV plus GS-4774 2, 10, or 40 yeast units (YU) subcutaneously every 4weeks until week 20. OAV was continued for the remainder of the study. Efficacy was measured by decline in serum hepatitis B surface antigen (HBsAg) from baseline to week 24.
  
  
  
  Baseline characteristics were similar across groups (mean age, 45-50years; male, 62-74%; Asian, 68-80%; hepatitis B e antigen (HBeAg)-positive, 24-26%; mean HBsAg, 2.5-3.1log10IU/ml). There were no significant differences between groups in mean HBsAg declines from baseline to week 24 or 48. Five HBeAg-positive patients receiving GS-4774 experienced HBeAg loss vs. none in the control group. Three GS-4774 40 YU-treated patients had HBsAg declines ⩾0.5log10IU/ml, but no patient experienced loss of serum HBsAg. No virologic breakthrough occurred. Injection site reactions were the most frequent adverse event (AE), and there were no treatment discontinuations.
  
  
  
  GS-4774 was well tolerated, but did not provide significant reductions in serum HBsAg in virally suppressed patients with chronic hepatitis B. Efficacy of GS-4774 in treatment-naïve patients remains to be determined.
  
  
  
  GS-4774 is a therapeutic vaccine designed to improve the immune response against hepatitis B virus (HBV) in patients who already have chronic infection with HBV. In this study, GS-4774 was safe and well tolerated in patients with chronic HBV infection receiving oral antiviral therapy, but did not result in a clinical benefit. Combination approaches with other agents, and evaluation in other populations of patients with HBV are ongoing to determine if GS-4774 might have a therapeutic benefit.
  
  
  
  NCT01943799.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI, USA. Electronic address: aslok@med.umich.edu.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lok
authors.affiliation: Department of Medicine, New York University Langone Medical Center, New York University School of Medicine, NY, USA.
authors.forename: Calvin Q
authors.initials: CQ
authors.lastname: Pan
authors.affiliation: Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.
authors.forename: Steven-Huy B
authors.initials: SH
authors.lastname: Han
authors.affiliation: San Jose Gastroenterology, San Jose, CA, USA.
authors.forename: Huy N
authors.initials: HN
authors.lastname: Trinh
authors.affiliation: Department of Medicine, Kaiser Permanente, San Francisco, CA, USA.
authors.forename: W Jeffrey
authors.initials: WJ
authors.lastname: Fessel
authors.affiliation: GlobeImmune, Louisville, CO, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Rodell
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Lanjia
authors.initials: L
authors.lastname: Lin
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Anuj
authors.initials: A
authors.lastname: Gaggar
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Department of Infectious Diseases, University of Parma, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Division of Gastroenterology and Hepatology, Tufts Medical Center, Boston, MA, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.affiliation: Auckland City Hospital, Auckland, New Zealand.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
mesh_terms: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: GS-4774; Hepatitis B e antigen; Hepatitis B surface antigen; Hepatitis B virus; Nucleoside/nucleotide analogue; Phase II