A Study of Response-Guided Duration of Combination Therapy With GS-9451, Pegasys® and Copegus® With and Without Tegobuvir (GS-9190) in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C
- Conditions
- Hepatitis C, Chronic
- Interventions
- Drug: GS-9451 placeboBiological: Pegasys®
- Registration Number
- NCT01271790
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of a 4-drug regimen with GS-9451 and Tegobuvir and 24 weeks of a 3-drug regimen of GS-9451 without Tegobuvir, all with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 245
- Adult subjects 18 to 70 years of age
- Chronic HCV infection for at least 6 months prior to Baseline (Day 1)
- Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis
- Monoinfection with HCV genotype 1a or 1b
- HCV treatment-naïve
- Body mass index (BMI) between 18 and 36 kg/m2
- Creatinine clearance ≥ 50 mL/min
- Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.
- Screening laboratory values within defined thresholds for alanine aminotransferase (ALT), aspartate aminotransferase (AST), leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH), potassium, magnesium
- Autoimmune disease
- Decompensated liver disease or cirrhosis
- Poorly controlled diabetes mellitus
- Severe psychiatric illness
- Severe chronic obstructive pulmonary disease (COPD)
- Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
- Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers)
- History of hemoglobinopathy
- Known retinal disease
- Subjects who are immunosuppressed
- Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse
- Subjects who are on or are expected to be on a potent cytochrome P450 (CYP) 3A4 or Pgp inhibitor, or a QT prolonging medication within 2 weeks of Baseline (Day 1) or during the study
- Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 Tegobuvir placebo GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 1 Copegus® GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 2 GS-9451 GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 2 Pegasys® GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 2 Copegus® GS-9451 (active) and Tegobuvir (GS-9190) placebo in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 3 Tegobuvir placebo Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 3 GS-9451 placebo Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 3 Pegasys® Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 1 Tegobuvir (GS-9190) GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 1 Pegasys® GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy Arm 3 Copegus® Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration Arm 1 GS-9451 GS-9451 and Tegobuvir (GS-9190) in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
- Primary Outcome Measures
Name Time Method Sustained virologic response 24 weeks of off-treatment follow-up Sustained virologic response (SVR) defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after treatment cessation
- Secondary Outcome Measures
Name Time Method Safety and tolerability of therapy Through treatment period and 24 weeks of off-treatment follow-up Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events
Emergence of viral resistance following initiation of therapy with GS 9190 and GS 9451 Through treatment period, 24 weeks of off-treatment follow-up, and up to 48 weeks of follow-up in the Resistance Registry Substudy Viral dynamics and steady state pharmacokinetics Through Week 4 of therapy Viral dynamics and steady state pharmacokinetics of GS 9190 and GS 9451 when administered in combination with PEG and RBV; measured by HCV RNA levels and plasma concentrations of GS-9190 and GS-9451 over time
Durability of response in subjects who achieve SVR 36 months following Week 72
Trial Locations
- Locations (142)
Henry Ford Health System-Columbus center
🇺🇸Novi, Michigan, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Medical Associates Research Group
🇺🇸San Diego, California, United States
University of Miami
🇺🇸Miami, Florida, United States
Kaiser Permanente
🇺🇸San Diego, California, United States
San Francisco Veterans Affairs Medical Center
🇺🇸San Francisco, California, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Brooke Army Medical Center
🇺🇸San Antonio, Texas, United States
Consultants for Clinical
🇺🇸Cincinnati, Ohio, United States
Research Specialists of Texas
🇺🇸Houston, Texas, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Amcare Research Inc.
🇺🇸Houston, Texas, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States
Columbia Medical Group, The Frist Clinic
🇺🇸Nashville, Tennessee, United States
Kelsey Research Foundation
🇺🇸Houston, Texas, United States
AKH der Stadt Wien
🇦🇹Vienna, Austria
University of Arizona
🇺🇸Tucson, Arizona, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
ID Care 105
🇺🇸Hillsborough, New Jersey, United States
Landeskrankenhaus Graz West
🇦🇹Graz, Austria
Ziekenhuis Netwerk Antwerpen
🇧🇪Antwerpen, Belgium
Wojewodzki Szpital Specjalistyczny im. K. Dluskiego Oddzial Obserwacyjno-Zakazny
🇵🇱Bialystok, Poland
Memphis Gastroenterology Group
🇺🇸Germantown, Tennessee, United States
Radomski Szpital Specjalistyczny im. Dr Tytusa Chalubinskiego Oddzial obserwacyjno-zakazny z odcinkiem jednego dnia leczenia chorob watroby
🇵🇱Radom, Poland
Digestive Health Specialists, PA
🇺🇸Tupelo, Mississippi, United States
University of Medicine and Dentistry of New Jersey
🇺🇸Newark, New Jersey, United States
Wilhelminenspital der Stadt Wien
🇦🇹Vienna, Austria
ULB Erasme
🇧🇪Brussels, Belgium
Comprehensive Clinical Research
🇺🇸Berlin, New Jersey, United States
UCL Saint Luc
🇧🇪Brussels, Belgium
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
🇵🇱Warszawa, Poland
Saint Louis University
🇺🇸St. Louis, Missouri, United States
Alabama Liver and Digestive Specialists
🇺🇸Montgomery, Alabama, United States
Digestive Health Specialists of the Southeast
🇺🇸Dothan, Alabama, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
eStudySite
🇺🇸Oceanside, California, United States
Bach and Godofsky Infectious Diseases
🇺🇸Bradenton, Florida, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
IGRF
🇺🇸Indianapolis, Indiana, United States
South Denver Gastroenterology
🇺🇸Englewood, Colorado, United States
Infectious Disease Specialists of Atlanta
🇺🇸Decatur, Georgia, United States
Synergy Clinical Research Center
🇺🇸National City, California, United States
South Florida Center of Gastroenterology, LLC
🇺🇸Wellington, Florida, United States
RESEARCH and EDUCATION, INC
🇺🇸San Diego, California, United States
Palmetto Research
🇺🇸Hialeah, Florida, United States
Emory University, Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
Liver Center of Atlanta
🇺🇸Atlanta, Georgia, United States
Partners in Internal Medicine, P.C.
🇺🇸Worcester, Massachusetts, United States
Dekalb Gastroenterology
🇺🇸Decatur, Georgia, United States
Digestive Disease Associates, PA
🇺🇸Baltimore, Maryland, United States
Options Health Research, LLC
🇺🇸Tulsa, Oklahoma, United States
Concorde Medical Group
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
NYU Hepatology Associates
🇺🇸New York, New York, United States
Binghamton Gastroenterology
🇺🇸Binghamton, New York, United States
Liver Institute of Virginia, Bon Secours
🇺🇸Newport News, Virginia, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
Asheville Gastroenterology Associates, P.A.
🇺🇸Asheville, North Carolina, United States
Albert Einstein Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Klinikum der Johann Wolfgang Goethe-Universität
🇩🇪Frankfurt/M, Germany
UZ Antwerp
🇧🇪Edegem, Belgium
Erasmus University Medical Center Rotterdam
🇳🇱Rotterdam, Netherlands
Beaujon Hospital
🇫🇷Clichy, France
LKH Innsbruck
🇦🇹Innsbruck, Austria
Digestive and Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Hôpital de la Croix Rousse
🇫🇷Lyon, France
Henri Mondor Hospital
🇫🇷Créteil, France
Centre Hospitalier Régional d'Orléans, Hôpital de la Source
🇫🇷Orléans, France
University hospital Heidelberg
🇩🇪Heidelberg, Germany
Advanced Liver Therapies
🇺🇸Houston, Texas, United States
Leber- und Studienzentrum am Checkpoint
🇩🇪Berlin, Germany
Krankenhaus der Elisabethinen Linz GmbH
🇦🇹Linz, Austria
Nancy University Hospital Center
🇫🇷Vandoeuvre, France
Hôpital Cochin
🇫🇷Paris, France
Hôpital de I´Archet 2, Service Hépatologie
🇫🇷Nice, France
Groupe Hospitalier du Haut Leveque
🇫🇷Pessac, France
Asklepios Klinik Sankt Georg
🇩🇪Hamburg, Germany
Radaboud University Nijmegen Medical Centre (UMC St Radboud)
🇳🇱Nijmegen, Netherlands
University Hospital Bonn
🇩🇪Bonn, Germany
University Hospital Essen
🇩🇪Essen, Germany
Johannes Gutenberg University Hospital
🇩🇪Mainz, Germany
Charite University Medicine
🇩🇪Berlin, Germany
University Hospital Freiburg
🇩🇪Freiburg, Germany
University Hospital Leipzig
🇩🇪Leipzig, Germany
Academisch Medisch Centrum Universiteit Van Amsterdam
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza Oddział Obserwacyjno-Zakazny
🇵🇱Bydgoszcz, Poland
Szpital Specjalistyczny w Chorzowie
🇵🇱Chorzow, Poland
Niepubliczny Zakład Opieki Zdrowotnej "Pol-SaNa-Med" Sp. z o.o.
🇵🇱Czeladź, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny
🇵🇱Warszawa, Poland
Barts and The London Hospital
🇬🇧London, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego
🇵🇱Wrocław, Poland
Saint Mary's Hosptial
🇬🇧London, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
University of Chicago
🇺🇸Chicago, Illinois, United States
Virginia Mason Medical Center, Digestive Disease Institute
🇺🇸Seattle, Washington, United States
Chelsea and Westminster Hospital
🇬🇧London, United Kingdom
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Avail Clinical Research, LLC
🇺🇸Deland, Florida, United States
Atlanta Gastroenterology Associates
🇺🇸Atlanta, Georgia, United States
Graves Gilbert Clinic
🇺🇸Bowling Green, Kentucky, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Gastroenterology Associates, LLC
🇺🇸Baton Rouge, Louisiana, United States
Gastrointestinal Associates, PA
🇺🇸Jackson, Mississippi, United States
MN Gastroenterology, P.A.
🇺🇸Plymouth, Minnesota, United States
Atlantic Research Affiliates, LLC
🇺🇸Morristown, New Jersey, United States
Cornell University Gastroenterology & Hepatology
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
UT Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
James H. Quillen VA Medical Center
🇺🇸Mountain Home, Tennessee, United States
Metropolitan Research
🇺🇸Fairfax, Virginia, United States
Medizinische Universität Graz
🇦🇹Graz, Austria
Centre Hospitalier Universitaire Sart Tilman Liège
🇧🇪Liège, Belgium
Saint Joseph Hospital
🇫🇷Marseille, France
Centre Hospitalier Universitaire de Strasbourg - Hôpital Civil
🇫🇷Strasbourg, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Kings College Hospital
🇬🇧London, United Kingdom
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱Lublin, Poland
Wojewodzki Szpital Zespolony w Kielcach
🇵🇱Kielce, Poland
Wojewodzki Specjalistyczny Szpital im. Dr Wl. Bieganskiego w Lodzi
🇵🇱Lodz, Poland
North Manchester General Hospital
🇬🇧Manchester, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
The North Texas Research Institute
🇺🇸Arlington, Texas, United States
Scientific Clinical Research, Inc c/o Segal Institute for Clinical Research
🇺🇸North Miami, Florida, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
UNM Health Sciences Center
🇺🇸Albuquerque, New Mexico, United States
University of Florida
🇺🇸Gainesville, Florida, United States
University of Wisconsin Hospital & Clinics
🇺🇸Madison, Wisconsin, United States
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom