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

NCT01225380 | Completed Phase 2 DMC

• 1 other identifier: GS-US-196-0123
• Study Type: interventional
• Target: 324
• Locations: 11 countries
• Sites: 114

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.

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

Outcome Measures

Primary Outcomes (1)

• Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation

  24 weeks of off-treatment follow-up

Secondary Outcomes (4)

• Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events

  Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up

• Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256

  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

• 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

  Through Week 4 of therapy

• Long-term assessment of plasma HCV RNA in subjects who achieve SVR

  36 months following Week 72

Study Arms (3)

Arm 1

EXPERIMENTAL

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; Drug: GS-9256; Biological: Pegasys®; Drug: Copegus®

Arm 2

EXPERIMENTAL

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; Drug: GS-9256; Biological: Pegasys®; Drug: Copegus®

Arm 3

PLACEBO COMPARATOR

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; Drug: GS-9256 placebo; Biological: Pegasys®; Drug: Copegus®

Interventions

GS-9190 DRUG

GS-9190 capsule, 20 mg BID, 16 or 24 weeks

Arm 1

GS-9256 DRUG

GS-9256 capsule, 150 mg BID, 16 or 24 weeks

Arm 1

Pegasys® BIOLOGICAL

peginterferon alfa-2a, (solution for injection) 180 µg/week, up to 48 weeks

Arm 1

Copegus® DRUG

ribavirin 200 mg tablet (weight based: 1000 mg/day \<75 kg; 1200 mg/day \>/= 75 kg) divided twice daily (BID), up to 48 weeks

Arm 1

GS-9190 placebo DRUG

placebo matching GS-9190 capsule BID, 24 weeks

Arm 2

GS-9256 placebo DRUG

placebo matching GS-9256 capsule BID, 24 weeks

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 ALT, 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 (114)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, 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

South Denver Gastroenterology

Englewood, Colorado, 80110, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami Center for Liver Diseases

Miami, Florida, 33136, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Bach and Godofsky Infectious Diseases

Sarasota, Florida, 34243, United States

Location

Atlanta Gastroenterology Associates

Atlanta, Georgia, 30308, United States

Location

Emory University, Infectious Disease Clinic

Atlanta, Georgia, 30308, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Gastroenterology Associates, LLC

Baton Rouge, Louisiana, 70809, United States

Location

Johns Hopkins University

Lutherville, Maryland, 21093, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Southwest CARE Center

Santa Fe, New Mexico, 87505, United States

Location

North Shore University Hospital

Great Neck, New York, 11021, United States

Location

Concorde Medical Group

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

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

University Gastroenterology

Providence, Rhode Island, 02905, United States

Location

Memphis Gastroenterology Group

Germantown, Tennessee, 38138, United States

Location

The North Texas Research Institute

Arlington, Texas, 76012, United States

Location

UT Southwestern Medical Center at Dallas

Dallas, Texas, 39090, United States

Location

Alamo Medical Research

San Antonio, Texas, 78215, 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

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

SGS - Clinical Pharmacology Unit Antwerpen

Antwerp, 2060, Belgium

Location

ULB Erasme

Brussels, 1070, Belgium

Location

UCL Saint Luc

Brussels, 1200, Belgium

Location

UZ Antwerp

Edegem, 2650, Belgium

Location

CHU Sart Tilman

Liège, 4000, Belgium

Location

Heritage Medical Research Clinic

Calgary, Alberta, T2N 4N1, Canada

Location

University of Alberta, Division of Gastroenterology

Edmonton, Alberta, T6G 2C2, Canada

Location

Downtown ID Clinic

Vancouver, British Columbia, V3S 4N9, Canada

Location

Gordon & Leslie Diamond Health Care Centre

Vancouver, British Columbia, V5Z 3P1, Canada

Location

GI Research Institute

Vancouver, British Columbia, V6Z 2K5, Canada

Location

John Buhler Research Centre

Winnipeg, Manitoba, R3E 3P4, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Ottawa Hospital, Division of Infectious Diseases

Ottawa, Ontario, K1H 8L6, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

University Hospital Brno

Brno, 625 00, Czechia

Location

Melnik Hospital

Mělník, 276 01, Czechia

Location

University Hospital Plzen

Pilsen, 304 60, Czechia

Location

Klinmed, s.r.o.

Prague, 128 00, Czechia

Location

Institute of Clinic and Experimental Medicine

Prague, 140 21, Czechia

Location

Association of Physicians for Infection Diseases

Ústí nad Labem, 477 01, Czechia

Location

Beaujon Hospital

Clichy, 92110, France

Location

Henri Mondor Hospital

Créteil, 94000, France

Location

Claude Huriez Hospital

Lille, 59000, France

Location

Hotel Dieu Hospital

Lyon, 69002, France

Location

Saint Joseph Hospital

Marseille, 13008, France

Location

Nancy University Hospital Center

Vandœuvre-lès-Nancy, 54500, France

Location

Charite University Medicine

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

Ifi - Institut fuer Interdisziplinaere Medizin - Studien und Projekte GmbH

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

Ludwig-Maximilians-University Munich

München, 81377, Germany

Location

Epatologia, Azienda Ospedaliero "Spedali Civili"

Brescia, 25123, Italy

Location

U.O. Gastroenterologia 1 - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Medicina Generale - Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

U. O. C. di Gastroenterologia - Azienda Ospedaliero-Universitaria Policlinico Paolo Giaccone

Palermo, 90127, Italy

Location

Unità di Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria

Parma, 43100, Italy

Location

Gastroepatologia - Azienda Ospedaliero-Universitaria S. Giovanni Battista

Torino, 10126, Italy

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 Zaklad Opieki Zdrowotnej "Pol-SaNa-Med" Spolka z ograniczona odpowiedzialnoscia

Czeladź, 41-250, Poland

Location

Wojewodzki Szpital Zespolony w Kielcach

Kielce, 25-736, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie

Krakow, 31-501, 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 Wojewodzki Szpital Zespolony w Szczecinie

Szczecin, 71-455, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial Dzienny

Warsaw, 01-201, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddział X

Warsaw, 01-201, Poland

Location

Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie

Warsaw, 02-507, Poland

Location

EMC Instytut Medyczny S.A.

Wroclaw, 50-220, Poland

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clínico Universitario San Cecilio

Granada, 18012, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28222, Spain

Location

Hospital Universitario Ntra. Sra. de Valme

Seville, 41014, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

North Manchester General Hospital

Greater Manchester, M8 5RB, 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

University College London Hospital

London, NW1 2BU, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Chelsea and Westminster Hospital

London, SW109NH, United Kingdom

Location

Institute of Cellular Medicine (Hepatology)

Newcastle upon Tyne, NE24HH, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

tegobuvir; GS-9256; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

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: October 18, 2010
• First Posted: October 21, 2010
• Study Start: October 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: September 1, 2013
• Last Updated: January 28, 2014

Record last verified: 2013-12

Locations

ES (6); BE (5); DE (11); CA (10); FR (6); AU (5); US (36); GB (9); CZ (6); PL (14); IT (6)