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

Chronic HBV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01943799
• Other study ID #: GS-US-330-0101
• Status: Completed
• Phase: Phase 2
• Start date: September 13, 2013
• Est. completion date: March 3, 2015

Study information

• Verified date: October 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: March 3, 2015
• Est. primary completion date: September 9, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic HBV Infection
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Biological:
• GS-4774
Administered as a subcutaneous injection every 4 weeks for a total of 6 doses

Drug:
• OAV Regimen
Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)

Locations

Country	Name	City	State
New Zealand	Auckland Clinical Studies	Grafton
United States	University of Michigan	Ann Arbor	Michigan
United States	Digestive Disease Associates, PA	Baltimore	Maryland
United States	Tufts Medical Center	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Henry Ford Hospital and Health System	Detroit	Michigan
United States	Medical Pro-care	Flushing	New York
United States	Dumont-UCLA Liver Transplant Center	Los Angeles	California
United States	North Shore LIJ Health System	Manhasset	New York
United States	University of Miami	Miami	Florida
United States	Bon Secours St. Mary's Hospital of Richmond	Newport News	Virginia
United States	Huntington Medical Research Institutes	Pasadena	California
United States	Kaiser Permanente	Sacramento	California
United States	St.Louis University	Saint Louis	Missouri
United States	Kaiser Permanente	San Diego	California
United States	Kaiser Permanente	San Francisco	California
United States	Silicon Valley Research Institute	San Jose	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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