Chronic Hepatitis B
Conditions
Keywords
Hepatitis B, HBV, GS-7340, TDF, Tenofovir disoproxil fumarate, Gilead, Viread
Brief summary
This is an open-label study evaluating multiple doses of GS-7340 versus Tenofovir disoproxil fumarate (TDF).
Detailed description
This is a randomized, open-label, active-controlled study whose primary objective is to evaluate the safety and efficacy of several doses of GS-7340. This study will evaluate the safety, viral kinetics, and antiviral activity of 4 different doses of GS-7340 over 28 days of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of GS-7340 versus 300mg Tenofovir disoproxil fumarate (TDF) over 28 days of therapy.
Interventions
DRUGGS-7340
Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
DRUGTenofovir disoproxil fumarate
Subjects will receive 300mg of Tenofovir disoproxil fumarate (TDF) over 28 days of therapy
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must be between 18 and 65 years of age * Must have Screening plasma HBV DNA ≥ 2x10\^3 IU/mL * Must have chronic HBV infection for at least 6 months * Must have estimated creatinine clearance (CLCr) ≥ 70 mL/min * Not pregnant or nursing * Women must be of non-childbearing potential OR of childbearing potential with confirmed negative pregnancy tests * Consistent and correct use of recommended methods of birth control for men and women
Exclusion criteria
* Pregnant or lactating subjects * Receipt of anti-HBV nucleoside/nucleotide therapy. Subjects who have failed prior Interferon treatment, greater than 6 months prior to screening, are permitted to participate in the study screening * Known co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV) * Presence of autoimmune disorders * History of liver disease other than Hepatitis B * History of Gilbert's Disease * Any sign of decompensated liver disease * Known or suspected cirrhosis * Evidence of hepatocellular carcinoma * Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities * Electrolyte abnormalities * History of treatment that permanently alters the gastric condition * Alcohol or substance abuse * History of bleeding diathesis * Significant bone disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum hepatitis B virus (HBV) DNA | Up to Week 4 | Time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40 and 120-mg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HBV DNA for tenofovir disoproxil fumarate (TDF) | Up to Week 4 | Comparing the short-term antiviral activity of GS-7340 with TDF 300mg. This is measured by time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for TDF. |
| Change in HBV DNA of GS-7340 through 28 days of therapy | Up to week 4 | Time weighted change from baseline to day 29 (DAVG4) in serum HBV DNA (log10 IU/mL) |
| Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF | Up to week 4 | GS-7340 and tenofovir (TFV) PK parameters in plasma will be calculated as applicable: Cmax, Tmax, Clast, Tlast, T1/2, λz, AUC0-t, AUC0-last, AUC0-∞, %AUCexp. PK samples are collected on: * Baseline/Day 1: 0 (predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose * Additional predose plasma samples will be collected on Days 2, 5, 8, 10, 15, 19, 22, and 29/End of Treatment. |
| Safety and Tolerability of Therapy | Up to week 4 | Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities |
Countries
Australia, Canada, New Zealand, United Kingdom, United States
Outcome results
None listed