A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B

• Change in HBV DNA for tenofovir disoproxil fumarate (TDF) [ Time Frame: Up to Week 4 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Up to week 4 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Up to week 4 ] [ Designated as safety issue: No ]

  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/ET.
• Safety and Tolerability of Therapy [ Time Frame: Up to week 4 ] [ Designated as safety issue: Yes ]
  Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities

This is an open-label study evaluating multiple doses of GS-7340 versus Tenofovir disoproxil fumarate (TDF).

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.

• Drug: GS-7340
  Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
  Other Name: GS-7340
• Drug: Tenofovir disoproxil fumarate
  Subjects will receive 300mg of Tenofovir disoproxil fumarate (TDF) over 28 days of therapy
  Other Name: Viread

• Experimental: GS-7340 8mg
  After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
  Intervention: Drug: GS-7340
• Experimental: GS-7340 25mg
  After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
  Intervention: Drug: GS-7340
• Experimental: GS-7340 40mg
  After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
  Intervention: Drug: GS-7340
• Experimental: GS-7340 120mg
  After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
  Intervention: Drug: GS-7340
• Experimental: Tenofovir disoproxil fumarate 300mg
  After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
  Intervention: Drug: Tenofovir disoproxil fumarate

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, HCV or 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