GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared With GS-5885, GS-9451 With Tegobuvir or RBV in Treatment-Experienced Subjects With Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection

This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared with GS-5885, GS-9451 with Tegobuvir or RBV in Treatment-Experienced Subjects with Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: GS-5885; Drug: GS-9451; Drug: tegobuvir; Drug: Ribavirin; Drug: placebo to match RBV; Drug: placebo to match tegobuvir

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10969
    • Leber- and Studienzentrum am Checkpoint
  • Berlin, Germany, 13353
    • Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn
  • Düsseldorf, Germany, 40237
    • Center for HIV and Hepatogastroenterology
  • Frankfurt, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe Universitaet
  • Freiburg, Germany, 79106
    • Medizinische Universitätsklinik
  • Hamburg, Germany, 22589
    • Universitätsklinikum Hamburg-Eppendorf
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Klinikum der Universität Heidelberg
  • Kiel, Germany, 24146
    • Gastroenterologisch-Hepatologisches Zentrum Kiel
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig
  • Mainz, Germany, 55131
    • Johannes Gutenberg University Hospital
  • Muenchen, Germany, 81377
    • Klinikum Innenstadt der LMU Munchen
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg - Med Klinik und Poliklinik
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute, LLC
    • Beverly Hills, California, United States, 90211
      • California Liver Institute
    • Coronado, California, United States, 92118
      • SCTI Research Foundation Liver Center
    • La Jolla, California, United States, 92161
      • University of California, San Diego
    • Los Angeles, California, United States, 90036
      • Lightsource Medical
    • San Diego, California, United States, 92123
      • Medical Associates Research Group, Inc.
    • San Diego, California, United States, 92154
      • Kaiser Permanente
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • San Jose, California, United States, 95128
      • San Jose Gastroenterology
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Whitman Walker Clinic
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Miami, Florida, United States, 33136
      • University of Miami, Center for Liver Diseases
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell Univeristy
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
  • Texas
    • Dallas, Texas, United States, 75204
      • Southwest Infectious Disease Clinical Research, Inc
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • The University of Texas Health Sciences Center at Houston
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research, Ltd.
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours St. Mary's Hospital of Richmond, Inc.
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years with chronic HCV infection
• Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
• Monoinfection with HCV genotype (GT) 1a or 1b
• HCV RNA ≥ 104 IU/mL at screening
• Prior treatment and adherence with one course of pegylated interferon alfa and RBV
• The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
• Body mass index (BMI) 18-40 kg/m2 inclusive

• Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)

  ≤ 450 msec for males and ≤ 470 msec for females.

• Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.

Exclusion Criteria:

• Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
• History of significant cardiac disease
• Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
• 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 resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
• Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID	Drug: GS-5885; Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD; Drug: GS-9451; Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD; Drug: tegobuvir; tegobuvir 30 mg BID; Drug: Ribavirin; Ribavirin (Copegus®) BID (1000 mg for subjects weighing < 75 kg and 1200 mg for subjects weighing ≥ 75 kg) divided BID
Active Comparator: Arm 2; GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID	Drug: GS-5885; Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD; Drug: GS-9451; Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD; Drug: tegobuvir; tegobuvir 30 mg BID; Drug: placebo to match RBV; Ribovirin placebo BID
Active Comparator: Arm 3; GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID	Drug: GS-5885; Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD; Drug: GS-9451; Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD; Drug: Ribavirin; Ribavirin (Copegus®) BID (1000 mg for subjects weighing < 75 kg and 1200 mg for subjects weighing ≥ 75 kg) divided BID; Drug: placebo to match tegobuvir; tegobuvir placebo BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.	24 weeks
Antiviral Activity	To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA < lower limit of quantitation [LLoQ] 24 weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and RBV compared with GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and RBV in treatment-experienced subjects with chronic genotype 1a or 1b HCV infection	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral Dynamics	To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir.	10 days
Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics	To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½	predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Antiviral Efficacy	To evaluate the antiviral efficacy (as defined by SVR) of adding pegylated interferon alfa-2a (PEG) and RBV (Arm 2 only) for 24-48 weeks to the original treatment regimen in subjects who experience viral breakthrough or relapse and enter the Rescue Therapy Substudy	24-48 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: John McNally, PhD, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: September 13, 2011
• First Submitted That Met QC Criteria: September 15, 2011
• First Posted (Estimate): September 16, 2011

Study Record Updates

• Last Update Posted (Estimate): December 17, 2013
• Last Update Submitted That Met QC Criteria: November 22, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: HCV; Treatment Experienced; Sustained Virologic Response; Hepatitis C; Combination Therapy; Protease inhibitor; Direct Acting Antiviral; GS-5885; Rapid Virologic Response; Tegobuvir; HCV RNA; Polymerase inhibitor; Interferon intolerant; Interferon ineligible; GS-9190; GS-9451; Chronic Genotype 1a or 1b
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Ledipasvir
• Other Study ID Numbers: GS-US-248-0131