The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
141
Sustained virologic response (SVR)
Time frame: 24 weeks of off-treatment follow-up
Safety and tolerability
To evaluate the safety and tolerability of 30 mg or 90 mg GS-5885 when given with GS-9451, Tegobuvir and RBV for 12 or 24 weeks. Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group.
Time frame: through 24 weeks of off-treatment follow-up
HCV RNA < Lower Limit Of Quantification
To evaluate the antiviral efficacy at Weeks 1, 2, 4, 12 and 24, as measured by the rates of HCV RNA \< LLoQ and viral breakthrough and relapse.
Time frame: Weeks 1, 2, 4, 12 and 24
Rescue Therapy Substudy SVR
To evaluate the antiviral efficacy (as defined by SVR) of the addition of pegylated interferon (PEG) for 24 weeks to GS-5885, GS-9451, tegobuvir and RBV in subjects who experience viral breakthrough on treatment.
Time frame: 24 Weeks
Emergence of viral resistance
To evaluate the emergence of viral resistance during treatment with GS-9451, Tegobuvir and RBV when given with 30 mg or 90 mg GS-5885 for 12 or 24 weeks.
Time frame: 12 or 24 weeks
Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV
HCV RNA levels, pharmacokinetics and viral sequencing
Time frame: Through Week 2 of therapy
Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV
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(weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
tablet, 90 mg QD
Birmingham Gastroenterology Associates, P.C.
Birmingham, Alabama, United States
Digestive Health Specialists of the Southeast
Dothan, Alabama, United States
Advanced Clinical Research Institute
Anaheim, California, United States
Southern California Liver Centers
Coronado, California, United States
UCSF Fresno Medical Education Program (MEP)
Fresno, California, United States
Stanford University School of Medicine
Palo Alto, California, United States
University of California San Diego
San Diego, California, United States
Kaiser Permanente
San Diego, California, United States
UCSF
San Francisco, California, United States
Walter Reed Army Medical Center
Washington D.C., District of Columbia, United States
...and 33 more locations
Pharmacokinetics (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885, GS-9451 and Tegobuvir using descriptive statistics (e.g., sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum). Plasma concentrations of the study drug over time will be summarized using descriptive statistics
Time frame: Through Week 2 of therapy