Efficacy and Safety Study of GS-9450 Treatment for 6 Months in Patients With Chronic Hepatitis C Virus Infection

January 3, 2014 updated by: Gilead Sciences

A Phase 2b, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of GS 9450 in Adults With Chronic Hepatitis C Virus Infection (GS-US-227-0106)

This is a Phase 2b, randomized, double-blind, parallel-group, placebo-controlled, multicenter study investigating the safety, tolerability and efficacy of two oral doses of GS-9450 in adults with chronic Hepatitis C Virus (HCV). Approximately 240 subjects 18-65 years of age who meet study entry criteria will be randomized (in other words, selected at random, like flipping a coin) to one of three treatment groups (80 subjects per treatment group) as follows:GS-9450 10 mg once daily,GS-9450 40 mg once daily, or matching placebo once daily.

Following randomization, subjects will return within seven business days for a Baseline (Day 1) visit, at which time study medication will be dispensed and subjects will enter a 26 week treatment phase. During the treatment phase, subjects will receive study drug once daily for 24 weeks and then taper off of study drug over the following 2 weeks by receiving study drug once every other day for one week and then every 3 days for one week. Following completion of the treatment phase, subjects will enter a 4-week off-treatment follow-up phase.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

307

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada
    • Ontario
      • London, Ontario, Canada
  • Germany
      • Berlin, Germany
      • Bonn, Germany
      • Essen, Germany
      • Frankfurt am Main, Germany
      • Hamburg, Germany
      • Hannover, Germany
      • Köln, Germany
      • Mainz, Germany
  • Poland
      • Bialystok, Poland
      • Bydgoszcz, Poland
      • Chorzów, Poland
      • Kielce, Poland
      • Wroclaw, Poland
  • Puerto Rico
      • San Juan, Puerto Rico
      • Santurce, Puerto Rico
  • United Kingdom
      • Brighton, United Kingdom
      • London, United Kingdom
      • Nottingham, United Kingdom
      • Sheffield, United Kingdom
  • United States
    • Arizona
      • Phoenix, Arizona, United States
      • Tucson, Arizona, United States
    • California
      • Anaheim, California, United States
      • Beverly Hills, California, United States
      • Cypress, California, United States
      • La Jolla, California, United States
      • Mission Hills, California, United States
      • Palm Springs, California, United States
      • Pasadena, California, United States
      • San Clemente, California, United States
      • San Diego, California, United States
    • District of Columbia
      • Washington, District of Columbia, United States
    • Florida
      • Hialeah, Florida, United States
      • Miami, Florida, United States
      • North Miami Beach, Florida, United States
      • Orlando, Florida, United States
      • Sarasota, Florida, United States
      • Tampa, Florida, United States
    • Georgia
      • Decatur, Georgia, United States
    • Illinois
      • Chicago, Illinois, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Kentucky
      • Louisville, Kentucky, United States
    • Louisiana
      • Baton Rouge, Louisiana, United States
      • New Orleans, Louisiana, United States
    • Maryland
      • Annapolis, Maryland, United States
      • Baltimore, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Michigan
      • Novi, Michigan, United States
      • St. Louis, Michigan, United States
    • Minnesota
      • Plymouth, Minnesota, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • Nevada
      • Las Vegas, Nevada, United States
    • New Jersey
      • Hillsborough, New Jersey, United States
      • Morristown, New Jersey, United States
    • New Mexico
      • Santa Fe, New Mexico, United States
    • New York
      • Johnson City, New York, United States
      • New York, New York, United States
      • Plainview, New York, United States
    • Ohio
      • Cincinnati, Ohio, United States
      • Cleveland, Ohio, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Rhode Island
      • Providence, Rhode Island, United States
    • Tennessee
      • Chattanooga, Tennessee, United States
      • Germantown, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • San Antonio, Texas, United States
    • Virginia
      • Fairfax, Virginia, United States
      • Falls Church, Virginia, United States
      • Norfolk, Virginia, United States
    • Washington
      • Seattle, Washington, United States
    • Wisconsin
      • Madison, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult subjects, ages 18-65
  • Chronic HCV infection, defined as having documented HCV infection (antibody or RNA positivity) at least 6 months prior to Baseline (Day 1) with HCV viremia at screening
  • Screening Knodell necroinflammatory score >= 3 based on liver biopsy evaluation (as determined by local pathologist) conducted anytime during the 45-day screening period
  • ALT > the upper limit of the normal range (ULN) but < 10 X ULN at the screening visit
  • Previously failed pegylated interferon-based HCV therapy in combination with ribavirin therapy, or is unable to tolerate or has contraindications to receiving interferon or ribavirin therapy
  • BMI between 19 and 36 kg/m2 (inclusive)
  • Creatinine clearance >= 70 mL/min
  • absolute neutrophil count >= 1000/mm3
  • Hemoglobin > 10 g/dL
  • Have no clinical or laboratory evidence of hepatic decompensation

Exclusion Criteria:

  • Decompensated liver disease
  • Child-Pugh grade B or C cirrhosis
  • Evidence of hepatocellular carcinoma
  • Positive urine drug screen for cocaine or amphetamines
  • Infection with HCV genotype 3
  • Co-infection with hepatitis B virus or human immunodeficiency virus
  • Pancreatitis
  • Recent significant infection or symptoms of infection
  • Autoimmune disorders
  • Any history of seizure
  • Is a public transportation operator (pilot of airplane or ship; air traffic controller; bus, train or subway driver) or operates heavy construction machinery
  • Transplantation
  • History of malignancy
  • Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males
  • History of or current binge drinking

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GS-9450 10 mg/day
GS-9450 taken as one 10 mg capsule by mouth once daily
Drug: GS-9450
Taken as one capsule by mouth once daily
Experimental: GS-9450 40 mg/day
GS-9450 taken as one 40 mg capsule by mouth once daily
Drug: GS-9450
Taken as one capsule by mouth once daily
Placebo Comparator: Placebo
Placebo taken as one placebo capsule by mouth once daily
Drug: Placebo
Taken as one placebo capsule (matching in appearance to GS-9450 capsules) by mouth once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 .
Time Frame: Week 24 on-treatment
Week 24 on-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change (absolute, percent) from baseline in the Knodell necroinflammatory score
Time Frame: Baseline to Week 24
Baseline to Week 24
Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels
Time Frame: Baseline to Week 24
Baseline to Week 24
Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities
Time Frame: Up to 24 weeks plus 30 days following the last dose of study drug
Up to 24 weeks plus 30 days following the last dose of study drug
Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels
Time Frame: Baseline to Week 24
Baseline to Week 24
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens
Time Frame: Baseline to Week 24
Baseline to Week 24
Change from baseline in the percent of apoptotic cells
Time Frame: Baseline to Week 24
Change from baseline in the percent of apoptotic cells (transferase deoxyuridine triphosphate [dUTP] nick end labeling [TUNEL] positive) as measured by TUNEL staining of liver biopsy specimens
Baseline to Week 24
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes
Time Frame: Baseline to Week 24
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes (for cytokeratin-18 neoantigen expression) as measured by immunohistochemical staining of liver biopsy specimens
Baseline to Week 24
Change From Baseline in HCV RNA
Time Frame: Baseline to to Week 24
Baseline to to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Investigators

  • Study Director: Ken Hirsch, MD, Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

April 2, 2009

First Submitted That Met QC Criteria

April 2, 2009

First Posted (Estimate)

April 3, 2009

Study Record Updates

Last Update Posted (Estimate)

February 4, 2014

Last Update Submitted That Met QC Criteria

January 3, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-227-0106

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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