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

Hepatitis C, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01271790
• Other study ID #: GS-US-196-0140
• Status: Completed
• Phase: Phase 2
• First received: January 5, 2011
• Last updated: January 8, 2014
• Start date: October 2010
• Est. completion date: September 2013

Study information

• Verified date: January 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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®).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 245
• Est. completion date: September 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Tegobuvir (GS-9190)
Tegobuvir (GS-9190) capsule, 30 mg BID
• 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)
• GS-9451
GS-9451 tablet, 200 mg QD
• Tegobuvir placebo
placebo matching Tegobuvir (GS-9190) capsule BID

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)
• Tegobuvir placebo
placebo matching Tegobuvir (GS-9190) capsule BID
• GS-9451 placebo
placebo matching GS-9451 tablet 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); tablet

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  France,  Germany,  Netherlands,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	Durability of response in subjects who achieve SVR		36 months following Week 72	No