A Study of Response-Guided Duration of Combination Therapy With GS-9190, GS-9256, Pegasys® and Copegus® in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C

Phase 2

Completed

Conditions: Chronic Hepatitis C Infection

Interventions: Drug: GS-9190
Drug: GS-9190 placebo
Drug: GS-9256
Drug: GS-9256 placebo
Biological: Pegasys®
Drug: Copegus®

Registration Number: NCT01225380

Lead Sponsor: Gilead Sciences

Brief Summary: This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of response-guided duration of therapy with GS-9190 and GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®). Additionally, the efficacy and safety of 24 weeks of GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) will be evaluated.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 324

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 ALT, 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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3	Pegasys®	Placebo matching GS-9190 and placebo matching GS-9256 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-9190	GS-9190 and GS-9256 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-9190 and GS-9256 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	Copegus®	GS-9190 and GS-9256 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-9190 placebo	GS-9256 (active) and placebo matching GS-9190 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	GS-9256	GS-9256 (active) and placebo matching GS-9190 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-9256 (active) and placebo matching GS-9190 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-9256 (active) and placebo matching GS-9190 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	GS-9190 placebo	Placebo matching GS-9190 and placebo matching GS-9256 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-9256 placebo	Placebo matching GS-9190 and placebo matching GS-9256 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration
Arm 3	Copegus®	Placebo matching GS-9190 and placebo matching GS-9256 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-9256	GS-9190 and GS-9256 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 (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation	24 weeks of off-treatment follow-up

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events	Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up
Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256	Through up to 48 weeks 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 of GS-9190 and GS-9256 when administered in combination with PEG and RBV; measured by HCV RNA levels and plasma concentrations of GS-9190 and GS-9256 over time	Through Week 4 of therapy
Long-term assessment of plasma HCV RNA in subjects who achieve SVR	36 months following Week 72	Plasma HCV RNA will be measured at approximately 6, 12, 24, and 36 months after Week 72.

Trial Locations

Locations (114): UT Southwestern Medical Center at Dallas
🇺🇸
Dallas, Texas, United States
Toronto General Hospital
🇨🇦
Toronto, Ontario, Canada
Medical Associates Research Group
🇺🇸
San Diego, California, United States
Kaiser Permanente
🇺🇸
San Diego, California, United States
University of Miami Center for Liver Diseases
🇺🇸
Miami, Florida, United States
Emory University, Infectious Disease Clinic
🇺🇸
Atlanta, Georgia, United States
Northwestern Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Alamo Medical Research
🇺🇸
San Antonio, Texas, United States
Virginia Mason Medical Center, Digestive Disease Institute
🇺🇸
Seattle, Washington, United States
UCL Saint Luc
🇧🇪
Brussels, Belgium
Medizinische Universität Graz
🇦🇹
Graz, Austria
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
🇵🇱
Krakow, Poland
ULB Erasme
🇧🇪
Brussels, Belgium
University of Alberta, Division of Gastroenterology
🇨🇦
Edmonton, Alberta, Canada
AKH der Stadt Wien
🇦🇹
Vienna, Austria
SGS - Clinical Pharmacology Unit Antwerpen
🇧🇪
Antwerpen, Belgium
University Hospital Plzen
🇨🇿
Plzen, Czech Republic
Gordon & Leslie Diamond Health Care Centre
🇨🇦
Vancouver, British Columbia, Canada
Wilhelminenspital der Stadt Wien
🇦🇹
Vienna, Austria
UZ Antwerp
🇧🇪
Edegem, Belgium
Association of Physicians for Infection Diseases
🇨🇿
Usti Nad labem, Czech Republic
Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
🇵🇱
Warszawa, Poland
Memphis Gastroenterology Group
🇺🇸
Germantown, Tennessee, United States
University Hospital Brno
🇨🇿
Brno, Czech Republic
Szpital Specjalistyczny w Chorzowie
🇵🇱
Chorzow, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddział X
🇵🇱
Warszawa, Poland
Mayo Clinic
🇺🇸
Phoenix, Arizona, United States
California Pacific Medical Center
🇺🇸
San Francisco, California, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Southwest CARE Center
🇺🇸
Santa Fe, New Mexico, United States
Advanced Clinical Research Institute
🇺🇸
Anaheim, California, United States
Johns Hopkins University
🇺🇸
Lutherville, Maryland, United States
South Denver Gastroenterology
🇺🇸
Englewood, Colorado, United States
Atlanta Gastroenterology Associates
🇺🇸
Atlanta, Georgia, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Gastroenterology Associates, LLC
🇺🇸
Baton Rouge, Louisiana, United States
Krankenhaus der Elisabethinen Linz GmbH
🇦🇹
Linz, Austria
Beaujon Hospital
🇫🇷
Clichy, France
Charite University Medicine
🇩🇪
Berlin, Germany
Derriford Hospital
🇬🇧
Plymouth, United Kingdom
University hospital Heidelberg
🇩🇪
Heidelberg, Germany
Johannes Gutenberg University Hospital
🇩🇪
Mainz, Germany
Melnik Hospital
🇨🇿
Melnik, Czech Republic
Downtown ID Clinic
🇨🇦
Vancouver, British Columbia, Canada
Medizinische Hochschule Hannover
🇩🇪
Hannover, Germany
University Hospital Leipzig
🇩🇪
Leipzig, Germany
Digestive and Liver Disease Specialists
🇺🇸
Norfolk, Virginia, United States
LKH Innsbruck
🇦🇹
Innsbruck, Austria
CHU Sart Tilman
🇧🇪
Liege, Belgium
Heritage Medical Research Clinic
🇨🇦
Calgary, Alberta, Canada
Ottawa Hospital, Division of Infectious Diseases
🇨🇦
Ottawa, Ontario, Canada
Klinmed, s.r.o.
🇨🇿
Prague, Czech Republic
Wojewodzki Szpital Specjalistyczny im. K. Dluskiego Oddzial Obserwacyjno-Zakazny
🇵🇱
Bialystok, Poland
Claude Huriez Hospital
🇫🇷
Lille, France
Saint Joseph Hospital
🇫🇷
Marseille, France
Nancy University Hospital Center
🇫🇷
Vandoeuvre, France
Toronto Western Hospital
🇨🇦
Toronto, Ontario, Canada
Hotel Dieu Hospital
🇫🇷
Lyon, France
Henri Mondor Hospital
🇫🇷
Créteil, France
Institute of Clinic and Experimental Medicine
🇨🇿
Prague, Czech Republic
University Hospital Freiburg
🇩🇪
Freiburg, Germany
University Hospital Essen
🇩🇪
Essen, Germany
Epatologia, Azienda Ospedaliero "Spedali Civili"
🇮🇹
Brescia, Italy
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza Oddział Obserwacyjno-Zakazny
🇵🇱
Bydgoszcz, Poland
Niepubliczny Zaklad Opieki Zdrowotnej "Pol-SaNa-Med" Spolka z ograniczona odpowiedzialnoscia
🇵🇱
Czeladz, Poland
U.O. Gastroenterologia 1 - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹
Milano, Italy
Medicina Generale - Azienda Ospedaliera di Padova
🇮🇹
Padova, Italy
Unità di Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria
🇮🇹
Parma, Italy
Gastroepatologia - Azienda Ospedaliero-Universitaria S. Giovanni Battista
🇮🇹
Torino, Italy
Wojewodzki Szpital Zespolony w Kielcach
🇵🇱
Kielce, Poland
Ifi - Institut fuer Interdisziplinaere Medizin - Studien und Projekte GmbH
🇩🇪
Hamburg, Germany
Ludwig-Maximilians-University Munich
🇩🇪
München, Germany
North Manchester General Hospital
🇬🇧
Greater Manchester, United Kingdom
Hospital Clínico Universitario San Cecilio
🇪🇸
Granada, Spain
Radomski Szpital Specjalistyczny im. Dr Tytusa Chalubinskiego Oddzial obserwacyjno-zakazny z odcinkiem jednego dnia leczenia chorob watroby
🇵🇱
Radom, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny
🇵🇱
Warszawa, Poland
EMC Instytut Medyczny S.A.
🇵🇱
Wroclaw, Poland
University College London Hospital
🇬🇧
London, United Kingdom
Kings College Hospital
🇬🇧
London, United Kingdom
Hospital Universitario Ntra. Sra. de Valme
🇪🇸
Sevilla, Spain
Hospital Universitari Vall d'Hebrón
🇪🇸
Barcelona, Spain
Institute of Cellular Medicine (Hepatology)
🇬🇧
Newcastle Upon Tyne, United Kingdom
Wojewodzki Specjalistyczny Szpital im. Dr Wl. Bieganskiego w Lodzi
🇵🇱
Lodz, Poland
Hospital Universitario Ramón y Cajal
🇪🇸
Madrid, Spain
Samodzielny Publiczny Wojewodzki Szpital Zespolony w Szczecinie
🇵🇱
Szczecin, Poland
Barts and The London Hospital
🇬🇧
London, United Kingdom
Queen Elizabeth Hospital
🇬🇧
Birmingham, United Kingdom
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Scripps Clinic
🇺🇸
La Jolla, California, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
North Shore University Hospital
🇺🇸
Great Neck, New York, United States
Concorde Medical Group
🇺🇸
New York, New York, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
University Gastroenterology
🇺🇸
Providence, Rhode Island, United States
John Buhler Research Centre
🇨🇦
Winnipeg, Manitoba, Canada
Metropolitan Research
🇺🇸
Fairfax, Virginia, United States
Bach and Godofsky Infectious Diseases
🇺🇸
Sarasota, Florida, United States
Cornell University Gastroenterology & Hepatology
🇺🇸
New York, New York, United States
The North Texas Research Institute
🇺🇸
Arlington, Texas, United States
Liver Institute of Virginia, Bon Secours
🇺🇸
Newport News, Virginia, United States
GI Research Institute
🇨🇦
Vancouver, British Columbia, Canada
London Health Sciences Centre
🇨🇦
London, Ontario, Canada
Klinikum der Johann Wolfgang Goethe-Universität
🇩🇪
Frankfurt/M, Germany
University Hospital Bonn
🇩🇪
Bonn, Germany
U. O. C. di Gastroenterologia - Azienda Ospedaliero-Universitaria Policlinico Paolo Giaccone
🇮🇹
Palermo, Italy
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱
Lublin, Poland
Hospital General Universitario de Valencia
🇪🇸
Valencia, Spain
Chelsea and Westminster Hospital
🇬🇧
London, United Kingdom
Orlando Immunology Center
🇺🇸
Orlando, Florida, United States
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸
Madrid, Spain
Royal Liverpool University Hospital
🇬🇧
Liverpool, United Kingdom