Safety and Efficacy of GS-4774 for the Treatment of Chronic Hepatitis B

A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B

The primary objectives of this study are to evaluate the safety and efficacy of GS-4774 in adults with chronic hepatitis B (CHB) viral infection who have been virally suppressed with an oral antiviral (OAV) medication.

Study Overview

• Status: Completed
• Conditions: Chronic HBV Infection
• Intervention / Treatment: Drug: OAV Regimen; Biological: GS-4774

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Grafton, New Zealand, 1141
    • Auckland Clinical Studies
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Dumont-UCLA Liver Transplant Center
    • Pasadena, California, United States, 91105
      • Huntington Medical Research Institutes
    • Sacramento, California, United States, 95825
      • Kaiser Permanente
    • San Diego, California, United States, 92154
      • Kaiser Permanente
    • San Francisco, California, United States, 94118
      • Kaiser Permanente
    • San Jose, California, United States, 95128
      • Silicon Valley Research Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates, PA
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital and Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • St.Louis University
  • New York
    • Flushing, New York, United States, 11355
      • Medical Pro-care
    • Manhasset, New York, United States, 11030
      • North Shore Lij Health System
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours St. Mary's Hospital of Richmond

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• Currently taking an approved HBV oral antiviral medication
• Documented evidence of chronic HBV infection (eg, HBsAg positive for more than 6 months)
• Virally-suppressed (HBV DNA below the lower limit of quantification (LLOQ) for ≥ 1 year)

Key Exclusion Criteria:

• Cirrhosis
• Inadequate liver function
• Co-infection with hepatitic C virus (HCV), HIV or hepatitic D virus (HDV)
• Evidence of hepatocellular carcinoma
• Significant cardiovascular, pulmonary, or neurological disease
• Females who are pregnant or may wish to become pregnant during the study
• Received solid organ or bone marrow transplant
• Use of another investigational agents within 3 months of screening
• Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
• History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease ulcerative colitis, autoimmune disease
• Known hypersensitivity to study drug, metabolites or formulation excipients
• Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Participants under evaluation for possible malignancy are not eligible.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OAV Alone; Participants will continue their prebaseline OAV regimen alone from baseline to Week 48.	Drug: OAV Regimen; Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
Experimental: OAV + GS-4774 2 YU; Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 2 yeast units (YU) from baseline to Week 20.	Drug: OAV Regimen; Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination); Biological: GS-4774; Administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Experimental: OAV + GS-4774 10 YU; Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20.	Drug: OAV Regimen; Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination); Biological: GS-4774; Administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Experimental: OAV + GS-4774 40 YU; Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20.	Drug: OAV Regimen; Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination); Biological: GS-4774; Administered as a subcutaneous injection every 4 weeks for a total of 6 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HBsAg at Week 24	The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.	Baseline; Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HBsAg at Week 12	The change from baseline to Week 12 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.	Baseline; Week 12
Change From Baseline in HBsAg at Week 48	The change from baseline to Week 48 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure.	Baseline; Week 48
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24	HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit.	Week 24
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48	HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit.	Week 48
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24	HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit.	Week 24
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48	HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit.	Week 48
Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48	HBsAg 1-log decline was defined as ≥ 1 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.	Baseline; Weeks 12, 24, and 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Lok AS, Pan CQ, Han SH, Trinh HN, Fessel WJ, Rodell T, Massetto B, Lin L, Gaggar A, Subramanian GM, McHutchison JG, Ferrari C, Lee H, Gordon SC, Gane EJ. Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B. J Hepatol. 2016 Sep;65(3):509-16. doi: 10.1016/j.jhep.2016.05.016. Epub 2016 May 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2013
• Primary Completion (Actual): September 9, 2014
• Study Completion (Actual): March 3, 2015

Study Registration Dates

• First Submitted: September 12, 2013
• First Submitted That Met QC Criteria: September 12, 2013
• First Posted (Estimate): September 17, 2013

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Hepatitis B (HBV); Oral antiviral (OAV); GS-4774
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis B, Chronic
• Other Study ID Numbers: GS-US-330-0101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No