Clinical trial NCT01271790: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: 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-9451
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-01-07
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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®).


Eligibility 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 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

Primary outcomes:
measure: Sustained virologic response
timeFrame: 24 weeks of off-treatment follow-up
Secondary outcomes:
measure: Safety and tolerability of therapy
timeFrame: Through treatment period and 24 weeks of off-treatment follow-up
measure: Emergence of viral resistance following initiation of therapy with GS 9190 and GS 9451
timeFrame: Through treatment period, 24 weeks of off-treatment follow-up, and up to 48 weeks of follow-up in the Resistance Registry Substudy
measure: Viral dynamics and steady state pharmacokinetics
timeFrame: Through Week 4 of therapy
measure: Durability of response in subjects who achieve SVR
timeFrame: 36 months following Week 72
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists of the Southeast
state: Alabama
city: Montgomery
country: United States
facility: Alabama Liver and Digestive Specialists
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Chula Vista
country: United States
facility: eStudySite
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: National City
country: United States
facility: Synergy Clinical Research Center
state: California
city: Oceanside
country: United States
facility: eStudySite
state: California
city: San Diego
country: United States
facility: RESEARCH and EDUCATION, INC
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco Veterans Affairs Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology
state: Colorado
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Bradenton
country: United States
facility: Bach and Godofsky Infectious Diseases
state: Florida
city: Deland
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hialeah
country: United States
facility: Palmetto Research
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: North Miami
country: United States
facility: Scientific Clinical Research, Inc c/o Segal Institute for Clinical Research
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Wellington
country: United States
facility: South Florida Center of Gastroenterology, LLC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Atlanta
country: United States
facility: Emory University, Infectious Disease Clinic
state: Georgia
city: Atlanta
country: United States
facility: Liver Center of Atlanta
state: Georgia
city: Decatur
country: United States
facility: Dekalb Gastroenterology
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: IGRF
state: Indiana
city: Bowling Green
country: United States
facility: Graves Gilbert Clinic
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baton Rouge
country: United States
facility: Gastroenterology Associates, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Digestive Disease Associates, PA
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: Partners in Internal Medicine, P.C.
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health System-Columbus center
state: Michigan
city: Plymouth
country: United States
facility: MN Gastroenterology, P.A.
state: Minnesota
city: Jackson
country: United States
facility: Gastrointestinal Associates, PA
state: Mississippi
city: Tupelo
country: United States
facility: Digestive Health Specialists, PA
state: Mississippi
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Hillsborough
country: United States
facility: ID Care 105
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Research Affiliates, LLC
state: New Jersey
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: UNM Health Sciences Center
state: New Mexico
city: Binghamton
country: United States
facility: Binghamton Gastroenterology
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Concorde Medical Group
state: New York
city: New York
country: United States
facility: NYU Hepatology Associates
state: New York
city: New York
country: United States
facility: Cornell University Gastroenterology & Hepatology
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates, P.A.
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Options Health Research, LLC
state: Oklahoma
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Mountain Home
country: United States
facility: James H. Quillen VA Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Columbia Medical Group, The Frist Clinic
state: Tennessee
city: Arlington
country: United States
facility: The North Texas Research Institute
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Kelsey Research Foundation
state: Texas
city: Houston
country: United States
facility: Advanced Liver Therapies
state: Texas
city: Houston
country: United States
facility: Research Specialists of Texas
state: Texas
city: Houston
country: United States
facility: Amcare Research Inc.
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: San Antonio
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Newport News
country: United States
facility: Liver Institute of Virginia, Bon Secours
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center, Digestive Disease Institute
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital & Clinics
state: Wisconsin
city: Graz
country: Austria
facility: Landeskrankenhaus Graz West
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Innsbruck
country: Austria
facility: LKH Innsbruck
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz GmbH
city: Vienna
country: Austria
facility: AKH der Stadt Wien
city: Vienna
country: Austria
facility: Wilhelminenspital der Stadt Wien
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen
city: Brussels
country: Belgium
facility: ULB Erasme
city: Brussels
country: Belgium
facility: UCL Saint Luc
city: Edegem
country: Belgium
facility: UZ Antwerp
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire Sart Tilman Liège
city: Clichy
country: France
facility: Beaujon Hospital
city: Créteil
country: France
facility: Henri Mondor Hospital
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Marseille
country: France
facility: Saint Joseph Hospital
city: Nice
country: France
facility: Hôpital de I´Archet 2, Service Hépatologie
city: Orléans
country: France
facility: Centre Hospitalier Régional d'Orléans, Hôpital de la Source
city: Paris
country: France
facility: Hôpital Cochin
city: Pessac
country: France
facility: Groupe Hospitalier du Haut Leveque
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire de Strasbourg - Hôpital Civil
city: Vandoeuvre
country: France
facility: Nancy University Hospital Center
city: Berlin
country: Germany
facility: Charite University Medicine
city: Berlin
country: Germany
facility: Leber- und Studienzentrum am Checkpoint
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Essen
country: Germany
facility: University Hospital Essen
city: Frankfurt/M
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Hamburg
country: Germany
facility: Asklepios Klinik Sankt Georg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: University hospital Heidelberg
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Mainz
country: Germany
facility: Johannes Gutenberg University Hospital
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum Universiteit Van Amsterdam
city: Nijmegen
country: Netherlands
facility: Radaboud University Nijmegen Medical Centre (UMC St Radboud)
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center Rotterdam
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Bialystok
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. K. Dluskiego Oddzial Obserwacyjno-Zakazny
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza Oddział Obserwacyjno-Zakazny
city: Chorzow
country: Poland
facility: Szpital Specjalistyczny w Chorzowie
city: Czeladź
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej "Pol-SaNa-Med" Sp. z o.o.
city: Kielce
country: Poland
facility: Wojewodzki Szpital Zespolony w Kielcach
city: Krakow
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
city: Lodz
country: Poland
facility: Wojewodzki Specjalistyczny Szpital im. Dr Wl. Bieganskiego w Lodzi
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
city: Radom
country: Poland
facility: Radomski Szpital Specjalistyczny im. Dr Tytusa Chalubinskiego Oddzial obserwacyjno-zakazny z odcinkiem jednego dnia leczenia chorob watroby
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
city: Wrocław
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Barts and The London Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: Saint Mary's Hosptial
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Gilead Sciences
name: Bittoo Kanwar
role: STUDY_DIRECTOR
References: