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

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating 16 and 24 Weeks of Four-Drug Regimen and 24 Weeks of a Three-Drug Regimen of GS-9451, Peginterferon Alfa 2a (PEG, Pegasys®) and Ribavirin (RBV, Copegus®) With and Without Tegobuvir (GS-9190) Followed by Response Guided PEG and RBV in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS US 196 0140

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®).

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Tegobuvir (GS-9190); Drug: GS-9451; Biological: Pegasys®; Drug: Copegus®; Drug: GS-9451; Drug: Copegus®; Drug: Tegobuvir placebo; Drug: GS-9451 placebo

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz
  • Graz, Austria, 8020
    • Landeskrankenhaus Graz West
  • Innsbruck, Austria, 6020
    • LKH Innsbruck
  • Linz, Austria, 4020
    • Krankenhaus der Elisabethinen Linz GmbH
  • Vienna, Austria, 1090
    • AKH der Stadt Wien
  • Vienna, Austria, 1171
    • Wilhelminenspital der Stadt Wien
• Belgium
  • Antwerpen, Belgium, 2060
    • Ziekenhuis Netwerk Antwerpen
  • Brussels, Belgium, 1070
    • ULB Erasme
  • Brussels, Belgium, 1200
    • UCL Saint Luc
  • Edegem, Belgium, 2650
    • UZ Antwerp
  • Liège, Belgium
    • Centre Hospitalier Universitaire Sart Tilman Liège
• France
  • Clichy, France, 92110
    • Beaujon Hospital
  • Créteil, France, 94010
    • Henri Mondor Hospital
  • Lyon, France, 69004
    • Hôpital de La Croix Rousse
  • Marseille, France, 13285
    • Saint Joseph Hospital
  • Nice, France, 06200
    • Hôpital de I´Archet 2, Service Hépatologie
  • Orléans, France, 45067
    • Centre Hospitalier Régional d'Orléans, Hôpital de la Source
  • Paris, France, 75679
    • Hôpital Cochin
  • Pessac, France, 33604
    • Groupe Hospitalier du Haut Leveque
  • Strasbourg, France, 67091
    • Centre Hospitalier Universitaire de Strasbourg - Hôpital Civil
  • Vandoeuvre, France, 54511
    • Nancy University Hospital Center
• Germany
  • Berlin, Germany, 13353
    • Charité University Medicine
  • Berlin, Germany, 13353
    • Leber- und Studienzentrum am Checkpoint
  • Bonn, Germany, 53105
    • University Hospital Bonn
  • Essen, Germany, 45122
    • University Hospital Essen
  • Frankfurt/M, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universität
  • Freiburg, Germany, 79106
    • University Hospital Freiburg
  • Hamburg, Germany, 20099
    • Asklepios Klinik Sankt Georg
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • University Hospital Heidelberg
  • Leipzig, Germany, 04103
    • University Hospital Leipzig
  • Mainz, Germany, 55131
    • Johannes Gutenberg University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum Universiteit van Amsterdam
  • Nijmegen, Netherlands, 6525 GA
    • Radaboud University Nijmegen Medical Centre (UMC St Radboud)
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus University Medical Center Rotterdam
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• Poland
  • Bialystok, Poland, 15-540
    • Wojewodzki Szpital Specjalistyczny im. K. Dluskiego Oddzial Obserwacyjno-Zakazny
  • Bydgoszcz, Poland, 85-030
    • Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza Oddział Obserwacyjno-Zakazny
  • Chorzow, Poland, 41-500
    • Szpital Specjalistyczny w Chorzowie
  • Czeladź, Poland, 41-250
    • Niepubliczny Zakład Opieki Zdrowotnej "Pol-SaNa-Med" Sp. z o.o.
  • Kielce, Poland, 25-317
    • Wojewodzki Szpital Zespolony w Kielcach
  • Krakow, Poland, 31-531
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
  • Lodz, Poland, 91-347
    • Wojewodzki Specjalistyczny Szpital im. Dr Wl. Bieganskiego w Lodzi
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Radom, Poland, 26-610
    • Radomski Szpital Specjalistyczny im. Dr Tytusa Chalubinskiego Oddzial obserwacyjno-zakazny z odcinkiem jednego dnia leczenia chorob watroby
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
  • Warszawa, Poland, 01-201
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny
  • Wrocław, Poland, 51-149
    • Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Liverpool, United Kingdom, L7 8XP UK
    • Royal Liverpool University Hospital
  • London, United Kingdom, SW10 9NH
    • Chelsea And Westminster Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, E1 2AT
    • Barts and The London Hospital
  • London, United Kingdom, NW1 2BU
    • Royal Free Hospital
  • London, United Kingdom, W2 1NY
    • Saint Mary's Hosptial
  • Manchester, United Kingdom, M13 9WL
    • Manchester Royal Infirmary
  • Manchester, United Kingdom, M8 5RB
    • North Manchester General Hospital
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals NHS Trust
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast
    • Montgomery, Alabama, United States, 36116
      • Alabama Liver and Digestive Specialists
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Medical Group
    • Chula Vista, California, United States, 91911
      • eStudySite
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • La Mesa, California, United States, 91942
      • eStudySite
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
    • Oceanside, California, United States, 92056
      • eStudySite
    • San Diego, California, United States, 92123
      • Medical Associates Research Group
    • San Diego, California, United States, 92154
      • Kaiser Permanente
    • San Diego, California, United States, 92015
      • RESEARCH and EDUCATION, INC
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • San Francisco, California, United States, 94121
      • San Francisco Veterans Affairs Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Englewood, Colorado, United States, 80110
      • South Denver Gastroenterology
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Bradenton, Florida, United States, 34209
      • Bach and Godofsky Infectious Diseases
    • Deland, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Hialeah, Florida, United States, 33016
      • Palmetto Research
    • Miami, Florida, United States, 33136
      • University of Miami
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc c/o Segal Institute for Clinical Research
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32804
      • Florida Hospital
    • Wellington, Florida, United States, 33414
      • South Florida Center of Gastroenterology, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Gastroenterology Associates
    • Atlanta, Georgia, United States, 30309
      • Liver Center of Atlanta
    • Atlanta, Georgia, United States, 30308
      • Emory University, Infectious Disease Clinic
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Decatur, Georgia, United States, 30033
      • Dekalb Gastroenterology
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46237
      • IGRF
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves Gilbert Clinic
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Gastroenterology Associates, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates, PA
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
    • Worcester, Massachusetts, United States, 01608
      • Partners in Internal Medicine, P.C.
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System-Columbus center
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • MN Gastroenterology, P.A.
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Gastrointestinal Associates, PA
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists, PA
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
    • Hillsborough, New Jersey, United States, 08844
      • ID Care 105
    • Morristown, New Jersey, United States, 07960
      • Atlantic Research Affiliates, LLC
    • Newark, New Jersey, United States, 07103
      • University of Medicine and Dentistry of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • UNM Health Sciences Center
  • New York
    • Binghamton, New York, United States, 13903
      • Binghamton Gastroenterology
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10016
      • Concorde Medical Group
    • New York, New York, United States, 10016
      • NYU Hepatology Associates
    • New York, New York, United States, 10021
      • Cornell University Gastroenterology & Hepatology
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, P.A.
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • Consultants for Clinical
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Memphis Gastroenterology Group
    • Mountain Home, Tennessee, United States, 37684
      • James H. Quillen VA Medical Center
    • Nashville, Tennessee, United States, 37203
      • Columbia Medical Group, The Frist Clinic
  • Texas
    • Arlington, Texas, United States, 76012
      • The North Texas Research Institute
    • Dallas, Texas, United States, 75390-8887
      • UT Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77005
      • Kelsey Research Foundation
    • Houston, Texas, United States, 77030
      • Research Specialists of Texas
    • Houston, Texas, United States, 77030
      • Advanced Liver Therapies
    • Houston, Texas, United States, 77090
      • Amcare Research Inc.
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
    • San Antonio, Texas, United States, 78234
      • Brooke Army Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Metropolitan Research
    • Newport News, Virginia, United States, 23602
      • Liver Institute of Virginia, Bon Secours
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center, Digestive Disease Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital & Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; 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	Drug: Tegobuvir (GS-9190); Tegobuvir (GS-9190) capsule, 30 mg BID; Drug: GS-9451; GS-9451 tablet, 200 mg once daily (QD); Biological: Pegasys®; peginterferon alfa-2a (solution for injection) 180 µg/week; Drug: Copegus®; ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); Drug: GS-9451; GS-9451 tablet, 200 mg QD; Drug: Copegus®; ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet
Active Comparator: Arm 2; 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	Drug: GS-9451; GS-9451 tablet, 200 mg once daily (QD); Biological: Pegasys®; peginterferon alfa-2a (solution for injection) 180 µg/week; Drug: Copegus®; ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); Drug: GS-9451; GS-9451 tablet, 200 mg QD; Drug: Copegus®; ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet; Drug: Tegobuvir placebo; placebo matching Tegobuvir (GS-9190) capsule BID
Placebo Comparator: Arm 3; 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	Biological: Pegasys®; peginterferon alfa-2a (solution for injection) 180 µg/week; Drug: Copegus®; ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); Drug: Copegus®; ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet; Drug: Tegobuvir placebo; placebo matching Tegobuvir (GS-9190) capsule BID; Drug: GS-9451 placebo; placebo matching GS-9451 tablet QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained virologic response	Sustained virologic response (SVR) defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after treatment cessation	24 weeks of off-treatment follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of therapy	Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events	Through treatment period and 24 weeks of off-treatment follow-up
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	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	Through Week 4 of therapy
Durability of response in subjects who achieve SVR		36 months following Week 72

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Bittoo Kanwar, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: January 5, 2011
• First Submitted That Met QC Criteria: January 6, 2011
• First Posted (Estimate): January 7, 2011

Study Record Updates

• Last Update Posted (Estimate): February 6, 2014
• Last Update Submitted That Met QC Criteria: January 8, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: HCV; Sustained Virologic Response; Hepatitis C; Combination Therapy; Protease inhibitor; Direct Acting Antiviral; Rapid Virologic Response; HCV RNA; Polymerase inhibitor; GS-9190; GS-9451; Treatment naïve
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Immunologic Factors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: GS-US-196-0140