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

Phase 2

Completed

• Conditions: Chronic HBV Infection
• Interventions: Biological: GS-4774; Drug: OAV Regimen

• Registration Number: NCT01943799
• Lead Sponsor: Gilead Sciences

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-09-12
• Study First Submitted QC: 2013-09-12
• Study Start: 2013-09-13
• Study First Posted: 2013-09-17
• Primary Completion: 2014-09-09
• Disposition First Submitted: 2015-01-16
• Disposition First Submitted QC: 2015-01-16
• Disposition First Posted: 2015-01-28
• Study Completion: 2015-03-03
• Status Verified: 2019-10
• Results First Submitted: 2019-10-03
• Results First Submitted QC: 2019-10-30
• Last Update Submitted: 2019-10-30
• Results First Posted: 2019-11-01
• Last Update Posted: 2019-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 178

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OAV + GS-4774 10 YU	GS-4774	Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20.
OAV + GS-4774 40 YU	OAV Regimen	Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20.
OAV + GS-4774 2 YU	GS-4774	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.
OAV + GS-4774 40 YU	GS-4774	Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20.
OAV Alone	OAV Regimen	Participants will continue their prebaseline OAV regimen alone from baseline to Week 48.
OAV + GS-4774 2 YU	OAV Regimen	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.
OAV + GS-4774 10 YU	OAV Regimen	Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in HBsAg at Week 24	Baseline; 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

Name	Time	Method
Change From Baseline in HBsAg at Week 12	Baseline; 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.
Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24	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 HBeAg Loss and HBeAg Seroconversion by Week 24	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.
Change From Baseline in HBsAg at Week 48	Baseline; 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 48	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 48	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	Baseline; 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.

Trial Locations

Locations (15)

Digestive Disease Associates, PA; 🇺🇸 Baltimore, Maryland, United States

St.Louis University; 🇺🇸 Saint Louis, Missouri, United States

Medical Pro-care; 🇺🇸 Flushing, New York, United States

North Shore LIJ Health System; 🇺🇸 Manhasset, New York, United States

Bon Secours St. Mary's Hospital of Richmond; 🇺🇸 Newport News, Virginia, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Hospital and Health System; 🇺🇸 Detroit, Michigan, United States

Auckland Clinical Studies; 🇳🇿 Grafton, New Zealand

Dumont-UCLA Liver Transplant Center; 🇺🇸 Los Angeles, California, United States

Kaiser Permanente; 🇺🇸 San Francisco, California, United States

Huntington Medical Research Institutes; 🇺🇸 Pasadena, California, United States

Silicon Valley Research Institute; 🇺🇸 San Jose, California, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States