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

Phase 2

Terminated

• Conditions: HCV Infection
• Interventions: Drug: GS-9450; Drug: Placebo

• Registration Number: NCT00874796
• Lead Sponsor: Gilead Sciences

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-04-02
• Study First Submitted QC: 2009-04-02
• Study First Posted: 2009-04-03
• Study Start: 2009-05
• Primary Completion: 2010-04
• Study Completion: 2010-07
• Status Verified: 2014-01
• Disposition First Submitted: 2014-01-03
• Disposition First Submitted QC: 2014-01-03
• Last Update Submitted: 2014-01-03
• Disposition First Posted: 2014-02-04
• Last Update Posted: 2014-02-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 307

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GS-9450 10 mg/day	GS-9450	GS-9450 taken as one 10 mg capsule by mouth once daily
GS-9450 40 mg/day	GS-9450	GS-9450 taken as one 40 mg capsule by mouth once daily
Placebo	Placebo	Placebo taken as one placebo capsule by mouth once daily

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change (absolute, percent) from baseline in the Knodell necroinflammatory score	Baseline to Week 24
Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels	Baseline to Week 24
Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities	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	Baseline to Week 24
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens	Baseline to Week 24
Change from baseline in the percent of apoptotic cells	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
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes	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
Change From Baseline in HCV RNA	Baseline to to Week 24