This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy using Combinations of Oral Antivirals (GS-5885, tegobuvir, and/or GS-9451) with Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection.
In September 2011, the FDA requested that Gilead make several major changes to this study because of side effects experienced by two patients in other Gilead studies. In 2 HCV-infected people that were given tegobuvir with another experimental medication plus interferon and ribavirin, big reductions in the number of white blood cells, red blood cells and platelets were seen. Because these cases might have been related to tegobuvir when given with interferon, ribavirin and another direct antiviral agent, tegobuvir is no longer being given to people with these other medications in this study. As a result, the study is now open label which means both you and your study doctor will know the medication you will be receiving and Arms 1 and 3 have been discontinued from the study. All subjects enrolled in the study as of September 2nd 2011 will receive Response Guided Therapy (RGT) with both GS-5885 and GS-9451 plus PEG and RBV.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
163
30 mg active tablet
two active 100 mg tablets
peginterferon alfa-2a (solution for injection) 180 µg/week
Sustained Virologic Response (SVR)
To evaluate antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< Lower Limit of Quantification (LLoQ) 24 weeks post-treatment) of response guided therapy (RGT) with GS-9451 + GS-5885, with peginterferon alfa-2a (PEG) and ribavirin (RBV) in treatment-experienced subjects.
Time frame: through 24 weeks of off-treatment follow-up
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.
Time frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
Safety and Tolerability
To evaluate the safety and tolerability of treatment with GS-5885, GS-9451, PEG \& RBV administered for 24 or 48 weeks. Safety endpoints will be summarized as the number (proportion) of subjects with events or abnormalities for categorical values or as an 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment arm.
Time frame: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV
HCV RNA levels, pharmacokinetics, and viral sequencing
Time frame: Through Week 2 of therapy
Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV
Plasma concentrations of the study drug over time will be summarized using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885 and GS-9451, using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum).
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ribavirin tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet
Digestive Health Specialists of the Southeast
Dothan, Alabama, United States
Alabama Liver and Digestive Specialists
Montgomery, Alabama, United States
California Liver Institute
Beverly Hills, California, United States
Scripps Clinic
La Jolla, California, United States
University of California Davis Medical Center
Sacramento, California, United States
RESEARCH and EDUCATION, INC
San Diego, California, United States
Medical Associates Research Group
San Diego, California, United States
Kaiser Permanente
San Diego, California, United States
University of Colorado Denver
Aurora, Colorado, United States
South Denver Gastroenterology
Englewood, Colorado, United States
...and 45 more locations
Time frame: Through Week 2 of therapy
Emergence of Viral Resistance
To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.
Time frame: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up