Clinical trial NCT01225380: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C Infection
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-9256
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-10-21
Enrollment: 324
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 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.


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 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

Primary outcomes:
measure: Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation
timeFrame: 24 weeks of off-treatment follow-up
Secondary outcomes:
measure: Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events
timeFrame: Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up
measure: Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256
timeFrame: 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
measure: 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
timeFrame: Through Week 4 of therapy
measure: Long-term assessment of plasma HCV RNA in subjects who achieve SVR
timeFrame: 36 months following Week 72
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
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: Englewood
country: United States
facility: South Denver Gastroenterology
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Center for Liver Diseases
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Sarasota
country: United States
facility: Bach and Godofsky Infectious Diseases
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: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baton Rouge
country: United States
facility: Gastroenterology Associates, LLC
state: Louisiana
city: Lutherville
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Great Neck
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: Cornell University Gastroenterology & Hepatology
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
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: San Antonio
country: United States
facility: Alamo Medical Research
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: 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: SGS - Clinical Pharmacology Unit Antwerpen
city: Brussels
country: Belgium
facility: ULB Erasme
city: Brussels
country: Belgium
facility: UCL Saint Luc
city: Edegem
country: Belgium
facility: UZ Antwerp
city: Liege
country: Belgium
facility: CHU Sart Tilman
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Division of Gastroenterology
state: Alberta
city: Vancouver
country: Canada
facility: Downtown ID Clinic
state: British Columbia
city: Vancouver
country: Canada
facility: Gordon & Leslie Diamond Health Care Centre
state: British Columbia
city: Vancouver
country: Canada
facility: GI Research Institute
state: British Columbia
city: Winnipeg
country: Canada
facility: John Buhler Research Centre
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital, Division of Infectious Diseases
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Brno
country: Czech Republic
facility: University Hospital Brno
city: Melnik
country: Czech Republic
facility: Melnik Hospital
city: Plzen
country: Czech Republic
facility: University Hospital Plzen
city: Prague
country: Czech Republic
facility: Klinmed, s.r.o.
city: Prague
country: Czech Republic
facility: Institute of Clinic and Experimental Medicine
city: Usti Nad labem
country: Czech Republic
facility: Association of Physicians for Infection Diseases
city: Clichy
country: France
facility: Beaujon Hospital
city: Créteil
country: France
facility: Henri Mondor Hospital
city: Lille
country: France
facility: Claude Huriez Hospital
city: Lyon
country: France
facility: Hotel Dieu Hospital
city: Marseille
country: France
facility: Saint Joseph Hospital
city: Vandoeuvre
country: France
facility: Nancy University Hospital Center
city: Berlin
country: Germany
facility: Charite University Medicine
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: Ifi - Institut fuer Interdisziplinaere Medizin - Studien und Projekte GmbH
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: München
country: Germany
facility: Ludwig-Maximilians-University Munich
city: Brescia
country: Italy
facility: Epatologia, Azienda Ospedaliero "Spedali Civili"
city: Milano
country: Italy
facility: U.O. Gastroenterologia 1 - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Padova
country: Italy
facility: Medicina Generale - Azienda Ospedaliera di Padova
city: Palermo
country: Italy
facility: U. O. C. di Gastroenterologia - Azienda Ospedaliero-Universitaria Policlinico Paolo Giaccone
city: Parma
country: Italy
facility: Unità di Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria
city: Torino
country: Italy
facility: Gastroepatologia - Azienda Ospedaliero-Universitaria S. Giovanni Battista
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: Czeladz
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej "Pol-SaNa-Med" Spolka z ograniczona odpowiedzialnoscia
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: Szczecin
country: Poland
facility: Samodzielny Publiczny Wojewodzki Szpital Zespolony w Szczecinie
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddział X
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny S.A.
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Granada
country: Spain
facility: Hospital Clínico Universitario San Cecilio
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Sevilla
country: Spain
facility: Hospital Universitario Ntra. Sra. de Valme
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Greater Manchester
country: United Kingdom
facility: North Manchester General 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: University College London Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Institute of Cellular Medicine (Hepatology)
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Gilead Sciences
name: Bittoo Kanwar
role: STUDY_DIRECTOR
References: