GS-5885, GS-9451 With Peginterferon Alfa 2a (PEG) and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 Hep C Virus Infection and IL28B CC Genotype

Phase 2

Terminated

Brief Summary: This is a Phase 2, randomized, open-label exploratory study that will examine the antiviral efficacy, safety, and tolerability of Response guided treatment (RGT) with GS-5885 + GS-9451 + PEG/RBV (6 or 12 weeks), or Peginterferon Alfa 2a (PEG)/Ribavirin (RBV)alone (24 weeks) in treatment naïve subjects with chronic Hep C (HCV) infection with genotype (GT) 1 and IL28B CC genotype.

Recruitment & Eligibility

Inclusion Criteria

Males and females 18-70 years of age
Chronic HCV infection
Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis. Alternatively a non-invasive alternative to liver biopsy (such as FibroTest, FibroScan, or Acoustic Radiation Force Impulse imaging) within 6 months of Screening in countries where allowed
Monoinfection with HCV genotype 1a or 1b
HCV RNA > 10^4 IU/mL at Screening
IL28B CC genotype
HCV treatment naïve
Candidate for PEG/RBV therapy
Body mass index (BMI) between 18 and 36 kg/m2
Creatinine clearance >= 50 mL/min
Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline

Exclusion Criteria

Exceed defined thresholds for key laboratory parameters at Screening
Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed
Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study
Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment

Arm && Interventions

Group	Intervention	Description
Arm 1	GS-5885	Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.
Arm 1	GS-9451	Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.
Arm 1	RBV	Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.
Arm 1	PEG	Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.
Arm 2	RBV	Response-Guided Therapy with PEG and RBV for 24 weeks.
Arm 2	PEG	Response-Guided Therapy with PEG and RBV for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Sustained virologic response (SVR)	30 , 36 or 48 weeks	Sustained virologic response (SVR, defined as plasma HCV RNA \< lower limit of quantification \[LLoQ\] at 24 weeks after treatment cessation) following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 or 12 weeks, or PEG/RBV for 24 weeks in IL28B CC subjects.

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of therapy	Up to 48 weeks	Safety and tolerability of the therapy is measured by frequency of laboratory abnormalities , reported adverse events and discontinuations due to adverse events.
Virologic response	Weeks 2, 4, 6, 8, 10, and 12	Virologic response at Weeks 2, 4, 6, 8, 10, and 12 (depending on treatment arm) as measured by the rates of HCV RNA \< LLoQ and viral breakthrough and relapse
Compare SVR	Weeks 30 and 36	Compare SVR following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 weeks versus 12 weeks.
Viral resistance	Up to 96 Weeks	Characterize viral resistance to GS-5885 and GS-9451 when administered in combination with PEG/RBV

Locations (54): Axis Clinical Trials
🇺🇸
Los Angeles, California, United States
UCLA Medical Center
🇺🇸
Los Angeles, California, United States
V.A. Greater Los Angeles Healthcare System
🇺🇸
Los Angeles, California, United States
UC Davis Medical Center
🇺🇸
Sacramento, California, United States
Research and Education, Inc.
🇺🇸
San Diego, California, United States
San Jose Gastroenterology
🇺🇸
San Jose, California, United States
Stanford University
🇺🇸
Stanford, California, United States
South Denver Gastroenterology
🇺🇸
Englewood, Colorado, United States
Indianapolis Gastroenterology Research Foundation
🇺🇸
Indianapolis, Indiana, United States
Commonwealth Clinical Studies, LLC
🇺🇸
Brockton, Massachusetts, United States
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Axis Clinical Trials
🇺🇸Los Angeles, California, United States