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

Chronic Hepatitis B Clinical Trial

Official title:

A Phase 1b Randomized, Open Label, Active-Controlled Study to Assess the Safety, Viral Kinetics, and Anti-HBV Activity of GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B (CHB) Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01671787
• Other study ID #: GS-US-320-0101
• Status: Completed
• Phase: Phase 1
• Start date: March 2012
• Est. completion date: April 2013

Study information

• Verified date: May 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Melborne	Victoria
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Austin Health	Melbourne	Victoria
Australia	Linear Clinical Research Ltd	Nedlands	Western Australia
Canada	Algorithme Pharma	Montreal	Quebec
Canada	The Ottawa Hospital, General Campus	Ottawa	Ontario
Canada	Pro-recherche	St. Romuald	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Downtown Infectious Diseases Clinic (University of British Columbia)	Vancouver	British Columbia
New Zealand	Auckland Clinical Studies	Auckland
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Grahame Hayton Unit	London
United Kingdom	Institute of Liver Studies, King's College Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust - Queens Medical Centre	Nottingham
United States	University of Maryland Institute of Human Virology	Baltimore	Maryland
United States	Henry Ford Health System	Detroit	Michigan
United States	Baylor College of Medicine - St. Luke's Episcopal Hospital	Houston	Texas
United States	Research and Education Inc.	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in serum hepatitis B virus (HBV) DNA	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.	Up to Week 4
Secondary	Change in HBV DNA for tenofovir disoproxil fumarate (TDF)	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.	Up to Week 4
Secondary	Change in HBV DNA of GS-7340 through 28 days of therapy	Time weighted change from baseline to day 29 (DAVG4) in serum HBV DNA (log10 IU/mL)	Up to week 4
Secondary	Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF	GS-7340 and tenofovir (TFV) PK parameters in plasma will be calculated as applicable: Cmax, Tmax, Clast, Tlast, T1/2, ?z, AUC0-t, AUC0-last, AUC0-8, %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.	Up to week 4
Secondary	Safety and Tolerability of Therapy	Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities	Up to week 4