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

NCT01271790 | Completed Phase 2 DMC

• 1 other identifier: GS-US-196-0140
• Study Type: interventional
• Target: 245
• Locations: 8 countries
• Sites: 144

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®).

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Safety and tolerability of therapy

  Through treatment period and 24 weeks of off-treatment follow-up

• 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

• Viral dynamics and steady state pharmacokinetics

  Through Week 4 of therapy

• Durability of response in subjects who achieve SVR

  36 months following Week 72

Study Arms (3)

Arm 1

ACTIVE COMPARATOR

GS-9451 and Tegobuvir (GS-9190) 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: Tegobuvir (GS-9190); Drug: GS-9451; Biological: Pegasys®; Drug: Copegus®

Arm 2

ACTIVE COMPARATOR

GS-9451 (active) and Tegobuvir (GS-9190) placebo 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-9451; Drug: Tegobuvir placebo; Biological: Pegasys®; Drug: Copegus®

Arm 3

PLACEBO COMPARATOR

Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration

Drug: Tegobuvir placebo; Drug: GS-9451 placebo; Biological: Pegasys®; Drug: Copegus®

Interventions

Tegobuvir (GS-9190) DRUG

Tegobuvir (GS-9190) capsule, 30 mg BID

Arm 1

GS-9451 DRUG

GS-9451 tablet, 200 mg once daily (QD)

Arm 1

Pegasys® BIOLOGICAL

peginterferon alfa-2a (solution for injection) 180 µg/week

Arm 1

Copegus® DRUG

ribavirin tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)

Arm 1

Tegobuvir placebo DRUG

placebo matching Tegobuvir (GS-9190) capsule BID

Arm 2

GS-9451 placebo DRUG

placebo matching GS-9451 tablet QD

Arm 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (144)

Digestive Health Specialists of the Southeast

Dothan, Alabama, 36305, United States

Location

Alabama Liver and Digestive Specialists

Montgomery, Alabama, 36116, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

Pacific Oaks Medical Group

Beverly Hills, California, 90211, United States

Location

eStudySite

Chula Vista, California, 91911, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

eStudySite

La Mesa, California, 91942, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Synergy Clinical Research Center

National City, California, 91950, United States

Location

eStudySite

Oceanside, California, 92056, United States

Location

RESEARCH and EDUCATION, INC

San Diego, California, 92015, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

Kaiser Permanente

San Diego, California, 92154, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

San Francisco Veterans Affairs Medical Center

San Francisco, California, 94121, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

South Denver Gastroenterology

Englewood, Colorado, 80110, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Bach and Godofsky Infectious Diseases

Bradenton, Florida, 34209, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Palmetto Research

Hialeah, Florida, 33016, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Scientific Clinical Research, Inc c/o Segal Institute for Clinical Research

North Miami, Florida, 33161, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Florida Hospital

Orlando, Florida, 32804, United States

Location

South Florida Center of Gastroenterology, LLC

Wellington, Florida, 33414, United States

Location

Atlanta Gastroenterology Associates

Atlanta, Georgia, 30308, United States

Location

Emory University, Infectious Disease Clinic

Atlanta, Georgia, 30308, United States

Location

Liver Center of Atlanta

Atlanta, Georgia, 30309, United States

Location

Dekalb Gastroenterology

Decatur, Georgia, 30033, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, 30033, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

IGRF

Indianapolis, Indiana, 46237, United States

Location

Graves Gilbert Clinic

Bowling Green, Kentucky, 42101, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Gastroenterology Associates, LLC

Baton Rouge, Louisiana, 70809, United States

Location

Digestive Disease Associates, PA

Baltimore, Maryland, 21229, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Partners in Internal Medicine, P.C.

Worcester, Massachusetts, 01608, United States

Location

Henry Ford Health System-Columbus center

Novi, Michigan, 48377, United States

Location

MN Gastroenterology, P.A.

Plymouth, Minnesota, 55446, United States

Location

Gastrointestinal Associates, PA

Jackson, Mississippi, 39202, United States

Location

Digestive Health Specialists, PA

Tupelo, Mississippi, 38801, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Comprehensive Clinical Research

Berlin, New Jersey, 08009, United States

Location

ID Care 105

Hillsborough, New Jersey, 08844, United States

Location

Atlantic Research Affiliates, LLC

Morristown, New Jersey, 07960, United States

Location

University of Medicine and Dentistry of New Jersey

Newark, New Jersey, 07103, United States

Location

UNM Health Sciences Center

Albuquerque, New Mexico, 87106, United States

Location

Binghamton Gastroenterology

Binghamton, New York, 13903, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Concorde Medical Group

New York, New York, 10016, United States

Location

NYU Hepatology Associates

New York, New York, 10016, United States

Location

Cornell University Gastroenterology & Hepatology

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Asheville Gastroenterology Associates, P.A.

Asheville, North Carolina, 28801, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Consultants for Clinical

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Options Health Research, LLC

Tulsa, Oklahoma, 74104, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Memphis Gastroenterology Group

Germantown, Tennessee, 38138, United States

Location

James H. Quillen VA Medical Center

Mountain Home, Tennessee, 37684, United States

Location

Columbia Medical Group, The Frist Clinic

Nashville, Tennessee, 37203, United States

Location

The North Texas Research Institute

Arlington, Texas, 76012, United States

Location

UT Southwestern Medical Center at Dallas

Dallas, Texas, 75390-8887, United States

Location

Kelsey Research Foundation

Houston, Texas, 77005, United States

Location

Advanced Liver Therapies

Houston, Texas, 77030, United States

Location

Research Specialists of Texas

Houston, Texas, 77030, United States

Location

Amcare Research Inc.

Houston, Texas, 77090, United States

Location

Alamo Medical Research

San Antonio, Texas, 78215, United States

Location

Brooke Army Medical Center

San Antonio, Texas, 78234, United States

Location

Metropolitan Research

Fairfax, Virginia, 22031, United States

Location

Liver Institute of Virginia, Bon Secours

Newport News, Virginia, 23602, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Virginia Mason Medical Center, Digestive Disease Institute

Seattle, Washington, 98101, United States

Location

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, 53792, United States

Location

Landeskrankenhaus Graz West

Graz, 8020, Austria

Location

Medizinische Universität Graz

Graz, 8036, Austria

Location

LKH Innsbruck

Innsbruck, 6020, Austria

Location

Krankenhaus der Elisabethinen Linz GmbH

Linz, 4020, Austria

Location

AKH der Stadt Wien

Vienna, 1090, Austria

Location

Wilhelminenspital der Stadt Wien

Vienna, 1171, Austria

Location

Ziekenhuis Netwerk Antwerpen

Antwerp, 2060, Belgium

Location

ULB Erasme

Brussels, 1070, Belgium

Location

UCL Saint Luc

Brussels, 1200, Belgium

Location

UZ Antwerp

Edegem, 2650, Belgium

Location

Centre Hospitalier Universitaire Sart Tilman Liège

Liège, Belgium

Location

Beaujon Hospital

Clichy, 92110, France

Location

Henri Mondor Hospital

Créteil, 94010, France

Location

Hôpital de la Croix Rousse

Lyon, 69004, France

Location

Saint Joseph Hospital

Marseille, 13285, France

Location

Hôpital de I´Archet 2, Service Hépatologie

Nice, 06200, France

Location

Centre Hospitalier Régional d'Orléans, Hôpital de la Source

Orléans, 45067, France

Location

Hôpital Cochin

Paris, 75679, France

Location

Groupe Hospitalier du Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Universitaire de Strasbourg - Hôpital Civil

Strasbourg, 67091, France

Location

Nancy University Hospital Center

Vandœuvre-lès-Nancy, 54511, France

Location

Charite University Medicine

Berlin, 13353, Germany

Location

Leber- und Studienzentrum am Checkpoint

Berlin, 13353, Germany

Location

University Hospital Bonn

Bonn, 53105, Germany

Location

University Hospital Essen

Essen, 45122, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universität

Frankfurt/M, 60590, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Asklepios Klinik Sankt Georg

Hamburg, 20099, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

University hospital Heidelberg

Heidelberg, 69120, Germany

Location

University Hospital Leipzig

Leipzig, 04103, Germany

Location

Johannes Gutenberg University Hospital

Mainz, 55131, Germany

Location

Academisch Medisch Centrum Universiteit Van Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

Radaboud University Nijmegen Medical Centre (UMC St Radboud)

Nijmegen, 6525 GA, Netherlands

Location

Erasmus University Medical Center Rotterdam

Rotterdam, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Wojewodzki Szpital Specjalistyczny im. K. Dluskiego Oddzial Obserwacyjno-Zakazny

Bialystok, 15-540, Poland

Location

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza Oddział Obserwacyjno-Zakazny

Bydgoszcz, 85-030, Poland

Location

Szpital Specjalistyczny w Chorzowie

Chorzów, 41-500, Poland

Location

Niepubliczny Zakład Opieki Zdrowotnej "Pol-SaNa-Med" Sp. z o.o.

Czeladź, 41-250, Poland

Location

Wojewodzki Szpital Zespolony w Kielcach

Kielce, 25-317, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

Krakow, 31-531, Poland

Location

Wojewodzki Specjalistyczny Szpital im. Dr Wl. Bieganskiego w Lodzi

Lodz, 91-347, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, 20-081, Poland

Location

Radomski Szpital Specjalistyczny im. Dr Tytusa Chalubinskiego Oddzial obserwacyjno-zakazny z odcinkiem jednego dnia leczenia chorob watroby

Radom, 26-610, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny

Warsaw, 01-201, Poland

Location

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie

Warsaw, 02-507, Poland

Location

Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego

Wroclaw, 51-149, Poland

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP UK, United Kingdom

Location

Barts and The London Hospital

London, E1 2AT, United Kingdom

Location

Royal Free Hospital

London, NW1 2BU, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Chelsea and Westminster Hospital

London, SW10 9NH, United Kingdom

Location

Saint Mary's Hosptial

London, W2 1NY, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

North Manchester General Hospital

Manchester, M8 5RB, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

tegobuvir; GS-9451; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Bittoo Kanwar

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2011
• First Posted: January 7, 2011
• Study Start: October 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: September 1, 2013
• Last Updated: February 6, 2014

Record last verified: 2014-01

Locations

PL (12); NL (4); US (85); FR (10); DE (11); GB (11); AU (6); BE (5)