This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared with GS-5885, GS-9451 with Tegobuvir or RBV in Treatment-Experienced Subjects with Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
170
Safety and Tolerability
To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
Time frame: 24 weeks
Antiviral Activity
To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< lower limit of quantitation \[LLoQ\] 24 weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and RBV compared with GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and RBV in treatment-experienced subjects with chronic genotype 1a or 1b HCV infection
Time frame: 24 weeks
Viral Dynamics
To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir.
Time frame: 10 days
Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics
To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½
Time frame: predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Antiviral Efficacy
To evaluate the antiviral efficacy (as defined by SVR) of adding pegylated interferon alfa-2a (PEG) and RBV (Arm 2 only) for 24-48 weeks to the original treatment regimen in subjects who experience viral breakthrough or relapse and enter the Rescue Therapy Substudy
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tegobuvir placebo BID
Ribovirin placebo BID
Ribavirin (Copegus®) BID (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) divided BID
University of Arizona
Tucson, Arizona, United States
Advanced Clinical Research Institute, LLC
Anaheim, California, United States
California Liver Institute
Beverly Hills, California, United States
SCTI Research Foundation Liver Center
Coronado, California, United States
University of California, San Diego
La Jolla, California, United States
Lightsource Medical
Los Angeles, California, United States
Medical Associates Research Group, Inc.
San Diego, California, United States
Kaiser Permanente
San Diego, California, United States
California Pacific Medical Center
San Francisco, California, United States
San Jose Gastroenterology
San Jose, California, United States
...and 41 more locations
Time frame: 24-48 weeks