search
Back to results

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

Primary Purpose

HCV Infection

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GS-9450
Placebo
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HCV Infection focused on measuring apoptosis, liver inflammation, hepatitis C

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

GS-9450 10 mg/day

GS-9450 40 mg/day

Placebo

Arm Description

GS-9450 taken as one 10 mg capsule by mouth once daily

GS-9450 taken as one 40 mg capsule by mouth once daily

Placebo taken as one placebo capsule by mouth once daily

Outcomes

Primary Outcome Measures

Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 .

Secondary Outcome Measures

Change (absolute, percent) from baseline in the Knodell necroinflammatory score
Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels
Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities
Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens
Change from baseline in the percent of apoptotic cells
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
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes
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
Change From Baseline in HCV RNA

Full Information

First Posted
April 2, 2009
Last Updated
January 3, 2014
Sponsor
Gilead Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT00874796
Brief Title
Efficacy and Safety Study of GS-9450 Treatment for 6 Months in Patients With Chronic Hepatitis C Virus Infection
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Terminated
Why Stopped
Reports of significant laboratory abnormalities and adverse events in a number of clinical study participants.
Study Start Date
May 2009 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HCV Infection
Keywords
apoptosis, liver inflammation, hepatitis C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
307 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GS-9450 10 mg/day
Arm Type
Experimental
Arm Description
GS-9450 taken as one 10 mg capsule by mouth once daily
Arm Title
GS-9450 40 mg/day
Arm Type
Experimental
Arm Description
GS-9450 taken as one 40 mg capsule by mouth once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo taken as one placebo capsule by mouth once daily
Intervention Type
Drug
Intervention Name(s)
GS-9450
Intervention Description
Taken as one capsule by mouth once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Taken as one placebo capsule (matching in appearance to GS-9450 capsules) by mouth once daily
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Change (absolute, percent) from baseline in the Knodell necroinflammatory score
Time Frame
Baseline to Week 24
Title
Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels
Time Frame
Baseline to Week 24
Title
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
Title
Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels
Time Frame
Baseline to Week 24
Title
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens
Time Frame
Baseline to Week 24
Title
Change from baseline in the percent of apoptotic cells
Description
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
Time Frame
Baseline to Week 24
Title
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes
Description
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
Time Frame
Baseline to Week 24
Title
Change From Baseline in HCV RNA
Time Frame
Baseline to to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ken Hirsch, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Anaheim
State/Province
California
Country
United States
City
Beverly Hills
State/Province
California
Country
United States
City
Cypress
State/Province
California
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
Mission Hills
State/Province
California
Country
United States
City
Palm Springs
State/Province
California
Country
United States
City
Pasadena
State/Province
California
Country
United States
City
San Clemente
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Hialeah
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
North Miami Beach
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Sarasota
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Decatur
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Baton Rouge
State/Province
Louisiana
Country
United States
City
New Orleans
State/Province
Louisiana
Country
United States
City
Annapolis
State/Province
Maryland
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Novi
State/Province
Michigan
Country
United States
City
St. Louis
State/Province
Michigan
Country
United States
City
Plymouth
State/Province
Minnesota
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
Las Vegas
State/Province
Nevada
Country
United States
City
Hillsborough
State/Province
New Jersey
Country
United States
City
Morristown
State/Province
New Jersey
Country
United States
City
Santa Fe
State/Province
New Mexico
Country
United States
City
Johnson City
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Plainview
State/Province
New York
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Providence
State/Province
Rhode Island
Country
United States
City
Chattanooga
State/Province
Tennessee
Country
United States
City
Germantown
State/Province
Tennessee
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Fairfax
State/Province
Virginia
Country
United States
City
Falls Church
State/Province
Virginia
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Madison
State/Province
Wisconsin
Country
United States
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Winnipeg
State/Province
Manitoba
Country
Canada
City
London
State/Province
Ontario
Country
Canada
City
Berlin
Country
Germany
City
Bonn
Country
Germany
City
Essen
Country
Germany
City
Frankfurt am Main
Country
Germany
City
Hamburg
Country
Germany
City
Hannover
Country
Germany
City
Köln
Country
Germany
City
Mainz
Country
Germany
City
Bialystok
Country
Poland
City
Bydgoszcz
Country
Poland
City
Chorzów
Country
Poland
City
Kielce
Country
Poland
City
Wroclaw
Country
Poland
City
San Juan
Country
Puerto Rico
City
Santurce
Country
Puerto Rico
City
Brighton
Country
United Kingdom
City
London
Country
United Kingdom
City
Nottingham
Country
United Kingdom
City
Sheffield
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs