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

Chronic Hepatitis C Infection Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01225380
• Other study ID #: GS-US-196-0123
• Status: Completed
• Phase: Phase 2
• First received: October 18, 2010
• Last updated: December 20, 2013
• Start date: October 2010
• Est. completion date: September 2013

Study information

• Verified date: December 2013
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• 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 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

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

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

Intervention

Drug:
• GS-9190
GS-9190 capsule, 20 mg BID, 16 or 24 weeks
• GS-9256
GS-9256 capsule, 150 mg BID, 16 or 24 weeks

Biological:
• Pegasys®
peginterferon alfa-2a, (solution for injection) 180 µg/week, up to 48 weeks

Drug:
• Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
• GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
• GS-9256
GS-9256 capsule, 150 mg BID, 24 weeks

Biological:
• Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, up to 48 weeks

Drug:
• Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
• GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
• GS-9256 placebo
placebo matching GS-9256 capsule BID, 24 weeks

Biological:
• Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, 48 weeks

Drug:
• Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), 48 weeks

Locations

Country	Name	City	State
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	SGS - Clinical Pharmacology Unit Antwerpen	Antwerpen
Belgium	UCL Saint Luc	Brussels
Belgium	ULB Erasme	Brussels
Belgium	UZ Antwerp	Edegem
Belgium	CHU Sart Tilman	Liege
Canada	Heritage Medical Research Clinic	Calgary	Alberta
Canada	University of Alberta, Division of Gastroenterology	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Ottawa Hospital, Division of Infectious Diseases	Ottawa	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Downtown ID Clinic	Vancouver	British Columbia
Canada	GI Research Institute	Vancouver	British Columbia
Canada	Gordon & Leslie Diamond Health Care Centre	Vancouver	British Columbia
Canada	John Buhler Research Centre	Winnipeg	Manitoba
Czech Republic	University Hospital Brno	Brno
Czech Republic	Melnik Hospital	Melnik
Czech Republic	University Hospital Plzen	Plzen
Czech Republic	Institute of Clinic and Experimental Medicine	Prague
Czech Republic	Klinmed, s.r.o.	Prague
Czech Republic	Association of Physicians for Infection Diseases	Usti Nad labem
France	Beaujon Hospital	Clichy
France	Henri Mondor Hospital	Créteil
France	Claude Huriez Hospital	Lille
France	Hotel Dieu Hospital	Lyon
France	Saint Joseph Hospital	Marseille
France	Nancy University Hospital Center	Vandoeuvre
Germany	Charite University Medicine	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	Ifi - Institut fuer Interdisziplinaere Medizin - Studien und Projekte GmbH	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	University hospital Heidelberg	Heidelberg
Germany	University Hospital Leipzig	Leipzig
Germany	Johannes Gutenberg University Hospital	Mainz
Germany	Ludwig-Maximilians-University Munich	München
Italy	Epatologia, Azienda Ospedaliero "Spedali Civili"	Brescia
Italy	U.O. Gastroenterologia 1 - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Medicina Generale - Azienda Ospedaliera di Padova	Padova
Italy	U. O. C. di Gastroenterologia - Azienda Ospedaliero-Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Unità di Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria	Parma
Italy	Gastroepatologia - Azienda Ospedaliero-Universitaria S. Giovanni Battista	Torino
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" Spolka z ograniczona odpowiedzialnoscia	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	Samodzielny Publiczny Wojewodzki Szpital Zespolony w Szczecinie	Szczecin
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	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zakazny Oddzial X	Warszawa
Poland	EMC Instytut Medyczny S.A.	Wroclaw
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Hospital Clínico Universitario San Cecilio	Granada
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Ntra. Sra. de Valme	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	North Manchester General Hospital	Greater Manchester
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	University College London Hospital	London
United Kingdom	Institute of Cellular Medicine (Hepatology)	Newcastle Upon Tyne
United Kingdom	Derriford Hospital	Plymouth
United States	Advanced Clinical Research Institute	Anaheim	California
United States	The North Texas Research Institute	Arlington	Texas
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Emory University, Infectious Disease Clinic	Atlanta	Georgia
United States	Gastroenterology Associates, LLC	Baton Rouge	Louisiana
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
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	North Shore University Hospital	Great Neck	New York
United States	Indiana University	Indianapolis	Indiana
United States	Scripps Clinic	La Jolla	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Johns Hopkins University	Lutherville	Maryland
United States	University of Miami Center for Liver Diseases	Miami	Florida
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	Liver Institute of Virginia, Bon Secours	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Orlando Immunology Center	Orlando	Florida
United States	Mayo Clinic	Phoenix	Arizona
United States	University Gastroenterology	Providence	Rhode Island
United States	Alamo Medical Research	San Antonio	Texas
United States	Kaiser Permanente	San Diego	California
United States	Medical Associates Research Group	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Bach and Godofsky Infectious Diseases	Sarasota	Florida
United States	Virginia Mason Medical Center, Digestive Disease Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation		24 weeks of off-treatment follow-up	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	Long-term assessment of plasma HCV RNA in subjects who achieve SVR	Plasma HCV RNA will be measured at approximately 6, 12, 24, and 36 months after Week 72.	36 months following Week 72	No