search
Back to results

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

Primary Purpose

Chronic HBV Infection

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GS-4774
OAV Regimen
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic HBV Infection focused on measuring Hepatitis B (HBV), Oral antiviral (OAV), GS-4774

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Dumont-UCLA Liver Transplant Center
  • Huntington Medical Research Institutes
  • Kaiser Permanente
  • Kaiser Permanente
  • Kaiser Permanente
  • Silicon Valley Research Institute
  • University of Miami
  • Northwestern Memorial Hospital
  • Digestive Disease Associates, PA
  • Tufts Medical Center
  • University of Michigan
  • Henry Ford Hospital and Health System
  • St.Louis University
  • Medical Pro-care
  • North Shore LIJ Health System
  • Bon Secours St. Mary's Hospital of Richmond
  • Auckland Clinical Studies

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

OAV Alone

OAV + GS-4774 2 YU

OAV + GS-4774 10 YU

OAV + GS-4774 40 YU

Arm Description

Participants will continue their prebaseline OAV regimen alone from baseline to Week 48.

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.

Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20.

Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 12, 2013
Last Updated
October 30, 2019
Sponsor
Gilead Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT01943799
Brief Title
Safety and Efficacy of GS-4774 for the Treatment of Chronic Hepatitis B
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
September 13, 2013 (Actual)
Primary Completion Date
September 9, 2014 (Actual)
Study Completion Date
March 3, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic HBV Infection
Keywords
Hepatitis B (HBV), Oral antiviral (OAV), GS-4774

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
178 (Actual)

8. Arms, Groups, and Interventions

Arm Title
OAV Alone
Arm Type
Experimental
Arm Description
Participants will continue their prebaseline OAV regimen alone from baseline to Week 48.
Arm Title
OAV + GS-4774 2 YU
Arm Type
Experimental
Arm Description
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.
Arm Title
OAV + GS-4774 10 YU
Arm Type
Experimental
Arm Description
Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20.
Arm Title
OAV + GS-4774 40 YU
Arm Type
Experimental
Arm Description
Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20.
Intervention Type
Biological
Intervention Name(s)
GS-4774
Intervention Description
Administered as a subcutaneous injection every 4 weeks for a total of 6 doses
Intervention Type
Drug
Intervention Name(s)
OAV Regimen
Intervention Description
Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)
Primary Outcome Measure Information:
Title
Change From Baseline in HBsAg at Week 24
Description
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.
Time Frame
Baseline; Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in HBsAg at Week 12
Description
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.
Time Frame
Baseline; Week 12
Title
Change From Baseline in HBsAg at Week 48
Description
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.
Time Frame
Baseline; Week 48
Title
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24
Description
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.
Time Frame
Week 24
Title
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24
Description
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.
Time Frame
Week 24
Title
Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48
Description
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.
Time Frame
Baseline; Weeks 12, 24, and 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Dumont-UCLA Liver Transplant Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Huntington Medical Research Institutes
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Kaiser Permanente
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States
Facility Name
Kaiser Permanente
City
San Diego
State/Province
California
ZIP/Postal Code
92154
Country
United States
Facility Name
Kaiser Permanente
City
San Francisco
State/Province
California
ZIP/Postal Code
94118
Country
United States
Facility Name
Silicon Valley Research Institute
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Digestive Disease Associates, PA
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Hospital and Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
St.Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Medical Pro-care
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
Facility Name
North Shore LIJ Health System
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Bon Secours St. Mary's Hospital of Richmond
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Auckland Clinical Studies
City
Grafton
ZIP/Postal Code
1141
Country
New Zealand

12. IPD Sharing Statement

Citations:
PubMed Identifier
27210427
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs