A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B
- Conditions
- Chronic Hepatitis B
- Interventions
- Registration Number
- NCT01671787
- Lead Sponsor
- Gilead Sciences
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 51
- Must be between 18 and 65 years of age
- Must have Screening plasma HBV DNA β₯ 2x10^3 IU/mL
- Must have chronic HBV infection for at least 6 months
- Must have estimated creatinine clearance (CLCr) β₯ 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GS-7340 8mg GS-7340 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. GS-7340 40mg GS-7340 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. GS-7340 25mg GS-7340 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. GS-7340 120mg GS-7340 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. Tenofovir disoproxil fumarate 300mg Tenofovir disoproxil fumarate 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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, Ξ»z, AUC0-t, AUC0-last, AUC0-β, %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
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.
Trial Locations
- Locations (19)
Institute of Liver Studies, King's College Hospital
π¬π§London, United Kingdom
Grahame Hayton Unit
π¬π§London, United Kingdom
Alfred Hospital
π¦πΊMelbourne, Victoria, Australia
Pro-recherche
π¨π¦St. Romuald, Quebec, Canada
University of Maryland Institute of Human Virology
πΊπΈBaltimore, Maryland, United States
University College London Hospital
π¬π§London, United Kingdom
Auckland Clinical Studies
π³πΏAuckland, New Zealand
Austin Health
π¦πΊMelbourne, Victoria, Australia
Monash Medical Centre
π¦πΊMelborne, Victoria, Australia
Downtown Infectious Diseases Clinic (University of British Columbia)
π¨π¦Vancouver, British Columbia, Canada
Nottingham University Hospitals NHS Trust - Queens Medical Centre
π¬π§Nottingham, United Kingdom
Research and Education Inc.
πΊπΈSan Diego, California, United States
Baylor College of Medicine - St. Luke's Episcopal Hospital
πΊπΈHouston, Texas, United States
Linear Clinical Research Ltd
π¦πΊNedlands, Western Australia, Australia
University Hospitals Birmingham NHS Foundation Trust
π¬π§Birmingham, United Kingdom
Algorithme Pharma
π¨π¦Montreal, Quebec, Canada
Toronto General Hospital
π¨π¦Toronto, Ontario, Canada
The Ottawa Hospital, General Campus
π¨π¦Ottawa, Ontario, Canada
Henry Ford Health System
πΊπΈDetroit, Michigan, United States