GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection

Phase 2

Completed

Interventions: Drug: GS-5885
Drug: GS-9451
Drug: tegobuvir
Drug: placebo to match tegobuvir
Drug: Ribavirin
Drug: placebo to match RBV

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

Age ≥18 years with chronic HCV infection
Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
Monoinfection with HCV genotype (GT) 1a or 1b
HCV RNA ≥ 104 IU/mL at screening
Prior treatment and adherence with one course of pegylated interferon alfa and RBV
The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
Body mass index (BMI) 18-40 kg/m2 inclusive
Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)

≤ 450 msec for males and ≤ 470 msec for females.
Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.

Exclusion Criteria

Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
History of significant cardiac disease
Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
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 resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.

Arm && Interventions

Group	Intervention	Description
Arm 1	GS-5885	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
Arm 1	GS-9451	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
Arm 1	tegobuvir	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
Arm 1	Ribavirin	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
Arm 2	GS-5885	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
Arm 2	GS-9451	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
Arm 2	tegobuvir	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
Arm 2	placebo to match RBV	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
Arm 3	GS-5885	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
Arm 3	GS-9451	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
Arm 3	placebo to match tegobuvir	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
Arm 3	Ribavirin	GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability	24 weeks	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.
Antiviral Activity	24 weeks	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

Secondary Outcome Measures

Name	Time	Method
Antiviral Efficacy	24-48 weeks	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
Viral Dynamics	10 days	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.
Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics	predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose	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

Locations (51): 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
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University of Arizona
🇺🇸Tucson, Arizona, United States