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 Infection
|Hepatitis C, Chronic||Drug: GS-5885 tablet Drug: GS-9451 tablet Biological: peginterferon alfa-2a Drug: ribavirin tablet||Phase 2|
|Study Design:||Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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 Infection (Protocol GS US 256 0124)|
- Sustained Virologic Response (SVR) [ Time Frame: through 24 weeks of off-treatment follow-up ]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.
- Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment ]To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.
- Safety and Tolerability [ Time Frame: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up ]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.
- Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV [ Time Frame: Through Week 2 of therapy ]HCV RNA levels, pharmacokinetics, and viral sequencing
- Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV [ Time Frame: Through Week 2 of therapy ]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).
- Emergence of Viral Resistance [ Time Frame: through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up ]To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.
|Study Start Date:||July 2011|
|Study Completion Date:||March 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm 2
AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food.
PM Dosing: RBV with food.
PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences.
Drug: GS-5885 tablet
30 mg active tabletDrug: GS-9451 tablet
two active 100 mg tabletsBiological: peginterferon alfa-2a
peginterferon alfa-2a (solution for injection) 180 µg/weekDrug: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01371578
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|Study Chair:||Bittoo Kanwar, MD||Gilead Sciences|