Overview

This trial is active, not recruiting.

Condition chronic hepatitis b
Treatments tdf, gs-4774
Phase phase 2
Sponsor Gilead Sciences
Start date August 2014
End date February 2016
Trial size 195 participants
Trial identifier NCT02174276, 2014-001011-39, GS-US-330-1401

Summary

This study is to evaluate the safety, tolerability, and efficacy of GS-4774 in adults with chronic hepatitis B infection (CHB) and who are currently not on treatment. Participants will be randomized to receive tenofovir disoproxil fumarate (TDF) alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will be discontinued. All participants will continue on TDF and will be followed for an additional 28 weeks. Following completion of the 48 week study period, all participants will be eligible for a 3 year registry study.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Participants will receive TDF for 48 weeks.
tdf Viread®
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily.
(Experimental)
Participants will receive TDF plus GS-4774 2 yeast units (YU) for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks.
tdf Viread®
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily.
gs-4774
GS-4774 administered as a subcutaneous injection every four weeks for a total of 6 doses
(Experimental)
Participants will receive TDF plus GS-4774 10 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks.
tdf Viread®
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily.
gs-4774
GS-4774 administered as a subcutaneous injection every four weeks for a total of 6 doses
(Experimental)
Participants will receive TDF plus GS-4774 40 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks.
tdf Viread®
Tenofovir disoproxil fumarate (TDF) 300 mg tablets administered orally once daily.
gs-4774
GS-4774 administered as a subcutaneous injection every four weeks for a total of 6 doses

Primary Outcomes

Measure
Mean change in serum hepatitis B surface antigen (HBsAg) from baseline to Week 24 (measured in log10 IU/mL)
time frame: Up to Week 24

Secondary Outcomes

Measure
Mean change in serum HBsAg from baseline to Weeks 12 and 48 (measured in log10 IU/mL)
time frame: Up to Week 48
Proportion of participants with HBsAg loss and HBsAg seroconversion at Weeks 24 and 48
time frame: Up to Week 48
Proportion of participants with a ≥ 0.5 log10 or a ≥ 1.0 log10 decline in HBsAg at Weeks 12, 24, and 48
time frame: Up to Week 48
Proportion of participants with hepatitis B e antigen (HBeAg) loss and HBeAg seroconversion at Weeks 24 and 48
time frame: Up to Week 48
Proportion of participants with hepatitis B virus (HBV) DNA < 20 IU/mL at Weeks 24 and 48
time frame: Up to Week 48
Proportions of participants experiencing virologic breakthrough at Weeks 24 and 48
time frame: Up to Week 48
Incidence of drug resistance mutations at Week 48
time frame: Up to Week 48

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study - Documented evidence of chronic HBV infection (e.g., HBsAg positive for more than 6 months) - Screening HBV DNA ≥ 2000 IU/mL - A negative serum pregnancy test is required for female subjects (unless surgically sterile or greater than two years post-menopausal) Exclusion Criteria: - Cirrhosis - Inadequate liver function - Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV) - Received antiviral treatment for HBV within 3 months of screening - Evidence of hepatocellular carcinoma (e.g., as evidenced by recent imaging) - Significant cardiovascular, pulmonary, or neurological disease - Women who are pregnant or may wish to become pregnant during the course of the study - Received solid organ or bone marrow transplant - Received prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics (e.g., monoclonal Ab, interferon) within 3 months of screening - Use of investigational agents within 3 months of screening - Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance - Receipt of immunoglobulin or other blood products within 3 months prior to enrollment - History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease, Ulcerative colitis, or autoimmune disease - Documented history of yeast allergy - Known hypersensitivity to study drugs, 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). Subjects under evaluation for possible malignancy are not eligible

Additional Information

Official title A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.