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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01225380
First received: October 18, 2010
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C Infection
Drug: GS-9190
Drug: GS-9256
Biological: Pegasys®
Drug: Copegus®
Drug: GS-9190 placebo
Drug: GS-9256 placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating 16 and 24 Weeks of Response Guided Therapy With GS-9190, GS-9256, Ribavirin (Copegus®) and Peginterferon Alfa 2a (Pegasys®) in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS-US-196-0123)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation [ Time Frame: 24 weeks of off-treatment follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events [ Time Frame: Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up ] [ Designated as safety issue: Yes ]
  • Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Through Week 4 of therapy ] [ Designated as safety issue: No ]
  • Long-term assessment of plasma HCV RNA in subjects who achieve SVR [ Time Frame: 36 months following Week 72 ] [ Designated as safety issue: No ]
    Plasma HCV RNA will be measured at approximately 6, 12, 24, and 36 months after Week 72.


Enrollment: 324
Study Start Date: October 2010
Study Completion Date: September 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
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
Drug: GS-9190
GS-9190 capsule, 20 mg BID, 16 or 24 weeks
Drug: GS-9256
GS-9256 capsule, 150 mg BID, 16 or 24 weeks
Biological: Pegasys®
peginterferon alfa-2a, (solution for injection) 180 µg/week, up to 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
Experimental: Arm 2
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
Drug: GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
Drug: GS-9256
GS-9256 capsule, 150 mg BID, 24 weeks
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, up to 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
Placebo Comparator: Arm 3
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
Drug: GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
Drug: GS-9256 placebo
placebo matching GS-9256 capsule BID, 24 weeks
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), 48 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225380

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic
Phoenix, Arizona, United States, 85054
United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
Scripps Clinic
La Jolla, California, United States, 92037
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Medical Associates Research Group
San Diego, California, United States, 92123
Kaiser Permanente
San Diego, California, United States, 92154
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Colorado
South Denver Gastroenterology
Englewood, Colorado, United States, 80110
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami Center for Liver Diseases
Miami, Florida, United States, 33136
Orlando Immunology Center
Orlando, Florida, United States, 32803
Bach and Godofsky Infectious Diseases
Sarasota, Florida, United States, 34243
United States, Georgia
Atlanta Gastroenterology Associates
Atlanta, Georgia, United States, 30308
Emory University, Infectious Disease Clinic
Atlanta, Georgia, United States, 30308
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Gastroenterology Associates, LLC
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Johns Hopkins University
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New Mexico
Southwest CARE Center
Santa Fe, New Mexico, United States, 87505
United States, New York
North Shore University Hospital
Great Neck, New York, United States, 11021
Mount Sinai Medical Center
New York, New York, United States, 10029
Cornell University Gastroenterology & Hepatology
New York, New York, United States, 10021
Concorde Medical Group
New York, New York, United States, 10016
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Rhode Island
University Gastroenterology
Providence, Rhode Island, United States, 02905
United States, Tennessee
Memphis Gastroenterology Group
Germantown, Tennessee, United States, 38138
United States, Texas
The North Texas Research Institute
Arlington, Texas, United States, 76012
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 39090
Alamo Medical Research
San Antonio, Texas, United States, 78215
United States, Virginia
Metropolitan Research
Fairfax, Virginia, United States, 22031
Liver Institute of Virginia, Bon Secours
Newport News, Virginia, United States, 23602
Digestive and Liver Disease Specialists
Norfolk, Virginia, United States, 23502
United States, Washington
Virginia Mason Medical Center, Digestive Disease Institute
Seattle, Washington, United States, 98101
Austria
Medizinische Universität Graz
Graz, Austria, 8036
LKH Innsbruck
Innsbruck, Austria, 6020
Krankenhaus der Elisabethinen Linz GmbH
Linz, Austria, 4020
AKH der Stadt Wien
Vienna, Austria, 1090
Wilhelminenspital der Stadt Wien
Vienna, Austria, 1171
Belgium
SGS - Clinical Pharmacology Unit Antwerpen
Antwerpen, Belgium, 2060
ULB Erasme
Brussels, Belgium, 1070
UCL Saint Luc
Brussels, Belgium, 1200
UZ Antwerp
Edegem, Belgium, 2650
CHU Sart Tilman
Liege, Belgium, 4000
Canada, Alberta
Heritage Medical Research Clinic
Calgary, Alberta, Canada, T2N 4N1
University of Alberta, Division of Gastroenterology
Edmonton, Alberta, Canada, T6G 2C2
Canada, British Columbia
Downtown ID Clinic
Vancouver, British Columbia, Canada, V3S 4N9
GI Research Institute
Vancouver, British Columbia, Canada, V6Z 2K5
Gordon & Leslie Diamond Health Care Centre
Vancouver, British Columbia, Canada, V5Z 3P1
Canada, Manitoba
John Buhler Research Centre
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5A5
Ottawa Hospital, Division of Infectious Diseases
Ottawa, Ontario, Canada, K1H 8L6
Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Czech Republic
University Hospital Brno
Brno, Czech Republic, 625 00
Melnik Hospital
Melnik, Czech Republic, 276 01
University Hospital Plzen
Plzen, Czech Republic, 304 60
Klinmed, s.r.o.
Prague, Czech Republic, 128 00
Institute of Clinic and Experimental Medicine
Prague, Czech Republic, 140 21
Association of Physicians for Infection Diseases
Usti Nad labem, Czech Republic, 477 01
France
Beaujon Hospital
Clichy, France, 92110
Henri Mondor Hospital
Créteil, France, 94000
Claude Huriez Hospital
Lille, France, 59000
Hotel Dieu Hospital
Lyon, France, 69002
Saint Joseph Hospital
Marseille, France, 13008
Nancy University Hospital Center
Vandoeuvre, France, 54500
Germany
Charite University Medicine
Berlin, Germany, 13353
University Hospital Bonn
Bonn, Germany, 53105
University Hospital Essen
Essen, Germany, 45122
Klinikum der Johann Wolfgang Goethe-Universität
Frankfurt/M, Germany, 60590
University Hospital Freiburg
Freiburg, Germany, 79106
Ifi - Institut fuer Interdisziplinaere Medizin - Studien und Projekte GmbH
Hamburg, Germany, 20099
Medizinische Hochschule Hannover
Hannover, Germany, 30625
University hospital Heidelberg
Heidelberg, Germany, 69120
University Hospital Leipzig
Leipzig, Germany, 04103
Johannes Gutenberg University Hospital
Mainz, Germany, 55131
Ludwig-Maximilians-University Munich
München, Germany, 81377
Italy
Epatologia, Azienda Ospedaliero "Spedali Civili"
Brescia, Italy, 25123
U.O. Gastroenterologia 1 - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milano, Italy, 20122
Medicina Generale - Azienda Ospedaliera di Padova
Padova, Italy, 35128
U. O. C. di Gastroenterologia - Azienda Ospedaliero-Universitaria Policlinico Paolo Giaccone
Palermo, Italy, 90127
Unità di Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria
Parma, Italy, 43100
Gastroepatologia - Azienda Ospedaliero-Universitaria S. Giovanni Battista
Torino, Italy, 10126
Poland
Wojewodzki Szpital Specjalistyczny im. K. Dluskiego Oddzial Obserwacyjno-Zakazny
Bialystok, Poland, 15-540
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza Oddział Obserwacyjno-Zakazny
Bydgoszcz, Poland, 85-030
Szpital Specjalistyczny w Chorzowie
Chorzow, Poland, 41-500
Niepubliczny Zaklad Opieki Zdrowotnej "Pol-SaNa-Med" Spolka z ograniczona odpowiedzialnoscia
Czeladz, Poland, 41-250
Wojewodzki Szpital Zespolony w Kielcach
Kielce, Poland, 25-736
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
Krakow, Poland, 31-501
Wojewodzki Specjalistyczny Szpital im. Dr Wl. Bieganskiego w Lodzi
Lodz, Poland, 91-347
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, Poland, 20-081
Radomski Szpital Specjalistyczny im. Dr Tytusa Chalubinskiego Oddzial obserwacyjno-zakazny z odcinkiem jednego dnia leczenia chorob watroby
Radom, Poland, 26-610
Samodzielny Publiczny Wojewodzki Szpital Zespolony w Szczecinie
Szczecin, Poland, 71-455
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny
Warszawa, Poland, 01-201
Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
Warszawa, Poland, 02-507
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddział X
Warszawa, Poland, 01-201
EMC Instytut Medyczny S.A.
Wroclaw, Poland, 50-220
Spain
Hospital Universitari Vall d'Hebrón
Barcelona, Spain, 08035
Hospital Clínico Universitario San Cecilio
Granada, Spain, 18012
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, Spain, 28222
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Hospital Universitario Ntra. Sra. de Valme
Sevilla, Spain, 41014
Hospital General Universitario de Valencia
Valencia, Spain, 46014
United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
North Manchester General Hospital
Greater Manchester, United Kingdom, M8 5RB
Royal Liverpool University Hospital
Liverpool, United Kingdom, L7 8XP UK
University College London Hospital
London, United Kingdom, NW1 2BU
Kings College Hospital
London, United Kingdom, SE5 9RS
Chelsea and Westminster Hospital
London, United Kingdom, SW109NH
Barts and The London Hospital
London, United Kingdom, E1 2AT
Institute of Cellular Medicine (Hepatology)
Newcastle Upon Tyne, United Kingdom, NE24HH
Derriford Hospital
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Bittoo Kanwar Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01225380     History of Changes
Other Study ID Numbers: GS-US-196-0123
Study First Received: October 18, 2010
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis C
HCV
Rapid Virologic Response
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
HCV RNA
Polymerase inhibitor
Protease inhibitor
Treatment naïve
GS-9190
GS-9256

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014