GS-5885, GS-9451 With Peginterferon Alfa 2a (PEG) and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 Hep C Virus Infection and IL28B CC Genotype

A Phase 2 Randomized, Open-Label, Exploratory Trial of GS-5885, GS-9451 With Peginterferon Alfa 2a and Ribavirin (RBV) in Treatment-Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection and IL28B CC Genotype

This is a Phase 2, randomized, open-label exploratory study that will examine the antiviral efficacy, safety, and tolerability of Response guided treatment (RGT) with GS-5885 + GS-9451 + PEG/RBV (6 or 12 weeks), or Peginterferon Alfa 2a (PEG)/Ribavirin (RBV)alone (24 weeks) in treatment naïve subjects with chronic Hep C (HCV) infection with genotype (GT) 1 and IL28B CC genotype.

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: GS-5885; Drug: GS-9451; Drug: RBV; Drug: PEG

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Concord, New South Wales, Australia, 2137
      • Concord Repatriation General Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • Saint Vincents Hospital
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Kogarah, New South Wales, Australia, NSW 2217
      • St. George Hospital
    • Sydney, New South Wales, Australia, 1871
      • Liverpool Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane Hospital Research Foundation
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Greenslopes Private Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital, Sydney Ltd.
    • Footscray, Victoria, Australia, VIC 3011
      • Western Hospital
    • Heidelberg, Victoria, Australia, 3081
      • Austin Health, Department of Hepatology
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3128
      • Box Hill Hospital
    • Melbourne, Victoria, Australia, 3004
      • Monash Medical Centre
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Fremantle Hospital
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N1
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2C8
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1H2
      • Lair Centre
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GIRI GI Research Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • University of Manitoba, John Buhler Research Centre
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • London Health Sciences
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
• New Zealand
  • Aukland, New Zealand
    • Auckland Hospital
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
• United States
  • California
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
    • Los Angeles, California, United States, 90073
      • V.A. Greater Los Angeles Healthcare System
    • Los Angeles, California, United States, 90057
      • Axis Clinical Trials
    • Los Angeles, California, United States, 90057
      • UCLA Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Diego, California, United States, 92105
      • Research and Education, Inc.
    • San Jose, California, United States, 95116
      • San Jose Gastroenterology
    • Stanford, California, United States, 94035
      • Stanford University
  • Colorado
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indianapolis Gastroenterology Research Foundation
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
      • Commonwealth Clinical Studies, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Impact Clinical Trials
  • New York
    • Great Neck, New York, United States, 11021
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • Weill Cornell College of Medicine
    • Yonkers, New York, United States, 10701
      • Westchester Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, P.A.
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Arlington, Texas, United States, 76012
      • The North Texas Research Institute
    • Houston, Texas, United States, 77030
      • Research Specialists of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • University of Utah Pediatric Pulmonology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Metropolitan Liver Diseases Center
    • Newport News, Virginia, United States, 23602
      • Liver Institute of Virginia, Bon Secours Health System
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 18-70 years of age
• Chronic HCV infection
• Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis. Alternatively a non-invasive alternative to liver biopsy (such as FibroTest, FibroScan, or Acoustic Radiation Force Impulse imaging) within 6 months of Screening in countries where allowed
• Monoinfection with HCV genotype 1a or 1b
• HCV RNA > 10^4 IU/mL at Screening
• IL28B CC genotype
• HCV treatment naïve
• Candidate for PEG/RBV therapy
• Body mass index (BMI) between 18 and 36 kg/m2
• Creatinine clearance >= 50 mL/min
• Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline

Exclusion Criteria:

• Exceed defined thresholds for key laboratory parameters at Screening
• Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed
• Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study
• Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.	Drug: GS-5885; GS-5885 30 mg tablet administered orally once daily; Drug: GS-9451; GS-9451 200 mg tablet administered orally once daily; Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
Experimental: Arm 2; Response-Guided Therapy with PEG and RBV for 24 weeks.	Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained virologic response (SVR)	Sustained virologic response (SVR, defined as plasma HCV RNA < lower limit of quantification [LLoQ] at 24 weeks after treatment cessation) following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 or 12 weeks, or PEG/RBV for 24 weeks in IL28B CC subjects.	30 , 36 or 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of therapy	Safety and tolerability of the therapy is measured by frequency of laboratory abnormalities , reported adverse events and discontinuations due to adverse events.	Up to 48 weeks
Virologic response	Virologic response at Weeks 2, 4, 6, 8, 10, and 12 (depending on treatment arm) as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse	Weeks 2, 4, 6, 8, 10, and 12
Compare SVR	Compare SVR following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 weeks versus 12 weeks.	Weeks 30 and 36
Viral resistance	Characterize viral resistance to GS-5885 and GS-9451 when administered in combination with PEG/RBV	Up to 96 Weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 27, 2011
• First Posted (Estimate): June 29, 2011

Study Record Updates

• Last Update Posted (Estimate): February 3, 2014
• Last Update Submitted That Met QC Criteria: January 2, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Chronic Hepatitis C; Treatment naive; Ribavirin (RBV); IL28B CC Genotype; Peginterferon α-2a (PEG); Genotype 1a/b; GS 9451; GS 5885; HCV NS5A inhibitor; HCV NS3 protease inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis, Chronic; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Ledipasvir
• Other Study ID Numbers: GS-US-248-0121