Clinical trial NCT00874796: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: HCV Infection
Keywords: apoptosis
liver inflammation
hepatitis C
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2009-04-03
Enrollment: 307
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 .
timeFrame: Week 24 on-treatment
Secondary outcomes:
measure: Change (absolute, percent) from baseline in the Knodell necroinflammatory score
timeFrame: Baseline to Week 24
measure: Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels
timeFrame: Baseline to Week 24
measure: Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities
timeFrame: Up to 24 weeks plus 30 days following the last dose of study drug
measure: Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels
timeFrame: Baseline to Week 24
measure: Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens
timeFrame: Baseline to Week 24
measure: Change from baseline in the percent of apoptotic cells
timeFrame: Baseline to Week 24
measure: Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes
timeFrame: Baseline to Week 24
measure: Change From Baseline in HCV RNA
timeFrame: Baseline to to Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Cypress
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Mission Hills
country: United States
state: California
city: Palm Springs
country: United States
state: California
city: Pasadena
country: United States
state: California
city: San Clemente
country: United States
state: California
city: San Diego
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Hialeah
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: North Miami Beach
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Annapolis
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Novi
country: United States
state: Michigan
city: St. Louis
country: United States
state: Michigan
city: Plymouth
country: United States
state: Minnesota
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Hillsborough
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: Santa Fe
country: United States
state: New Mexico
city: Johnson City
country: United States
state: New York
city: New York
country: United States
state: New York
city: Plainview
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Chattanooga
country: United States
state: Tennessee
city: Germantown
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Falls Church
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: London
country: Canada
state: Ontario
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
Study officials:
affiliation: Gilead Sciences
name: Ken Hirsch, MD
role: STUDY_DIRECTOR
References: