GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection
- Conditions
- Hepatitis C, Chronic
- Interventions
- Drug: placebo to match tegobuvirDrug: placebo to match RBV
- Registration Number
- NCT01435226
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 170
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- 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
Trial Locations
- Locations (51)
Advanced Clinical Research Institute, LLC
🇺🇸Anaheim, California, United States
Lightsource Medical
🇺🇸Los Angeles, California, United States
Medical Associates Research Group, Inc.
🇺🇸San Diego, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of Miami, Center for Liver Diseases
🇺🇸Miami, Florida, United States
Infectious Disease Specialists of Atlanta
🇺🇸Decatur, Georgia, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Southwest Infectious Disease Clinical Research, Inc
🇺🇸Dallas, Texas, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Therapeutic Concepts, PA
🇺🇸Houston, Texas, United States
The University of Texas Health Sciences Center at Houston
🇺🇸Houston, Texas, United States
Alamo Medical Research, Ltd.
🇺🇸San Antonio, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
California Liver Institute
🇺🇸Beverly Hills, California, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
SCTI Research Foundation Liver Center
🇺🇸Coronado, California, United States
Bon Secours St. Mary's Hospital of Richmond, Inc.
🇺🇸Newport News, Virginia, United States
Center for HIV and Hepatogastroenterology
🇩🇪Düsseldorf, Germany
Klinikum der Johann Wolfgang Goethe Universitaet
🇩🇪Frankfurt, Germany
Gastro One
🇺🇸Germantown, Tennessee, United States
Gastroenterologisch-Hepatologisches Zentrum Kiel
🇩🇪Kiel, Germany
Johannes Gutenberg University Hospital
🇩🇪Mainz, Germany
Medizinische Universitatsklinik
🇩🇪Freiburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
Leber- and Studienzentrum am Checkpoint
🇩🇪Berlin, Germany
Universitatsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Klinikum der Universität Heidelberg
🇩🇪Heidelberg, Germany
Henry Ford Health System
🇺🇸Novi, Michigan, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
Avail Clinical Research, LLC
🇺🇸DeLand, Florida, United States
Klinikum Innenstadt der LMU Munchen
🇩🇪Muenchen, Germany
Universitätsklinikum Würzburg - Med Klinik und Poliklinik
🇩🇪Würzburg, Germany
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Kaiser Permanente
🇺🇸San Diego, California, United States
San Jose Gastroenterology
🇺🇸San Jose, California, United States
Digestive and Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Whitman Walker Clinic
🇺🇸Washington, District of Columbia, United States
Johns Hopkins University
🇺🇸Lutherville, Maryland, United States
Weill Medical College of Cornell Univeristy
🇺🇸New York, New York, United States
Charite - Universitatsmedizin Berlin Campus Virchow-Klinikum
🇩🇪Berlin, Germany
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Montefiore Medical Center
🇺🇸Bronx, New York, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States