Anna S Lok1, Calvin Q Pan2, Steven-Huy B Han3, Huy N Trinh4, W Jeffrey Fessel5, Timothy Rodell6, Benedetta Massetto7, Lanjia Lin7, Anuj Gaggar7, G Mani Subramanian7, John G McHutchison7, Carlo Ferrari8, Hannah Lee9, Stuart C Gordon10, Edward J Gane11. 1. Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI, USA. Electronic address: aslok@med.umich.edu. 2. Department of Medicine, New York University Langone Medical Center, New York University School of Medicine, NY, USA. 3. Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA. 4. San Jose Gastroenterology, San Jose, CA, USA. 5. Department of Medicine, Kaiser Permanente, San Francisco, CA, USA. 6. GlobeImmune, Louisville, CO, USA. 7. Gilead Sciences, Inc., Foster City, CA, USA. 8. Department of Infectious Diseases, University of Parma, Italy. 9. Division of Gastroenterology and Hepatology, Tufts Medical Center, Boston, MA, USA. 10. Division of Gastroenterology, Henry Ford Hospital, Detroit, MI, USA. 11. Auckland City Hospital, Auckland, New Zealand.
Abstract
BACKGROUND & AIMS: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. METHODS: 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) tocontinue 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. RESULTS: 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. CONCLUSIONS: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. LAY SUMMARY: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 receivingoral 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. CLINICAL TRIAL REGISTRATION NUMBER: NCT01943799.
RCT Entities:
BACKGROUND & AIMS: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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. LAY SUMMARY: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. CLINICAL TRIAL REGISTRATION NUMBER: NCT01943799.