Chronic Hepatitis C Virus Infection MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Product Name: GS-9450
Product Code: GS-9450
Pharmaceutical Form: Capsule, hard
Current Sponsor code: GS-9450
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Cur
Sponsors
Gilead Sciences, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female, aged from 18 to 65 years old, inclusive • 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 (i.e., detectable plasma HCV RNA levels) at screening. • Documented evidence of either 1) having previously failed treatment with PEG-based HCV therapy in combination with RIBA therapy, OR 2) being unable to tolerate or having contraindications to receiving INF or RIBA therapy • Have a Knodell necroinflammatory score at least 3 as determined from the screening liver biopsy evaluation • Have laboratory values at Screen that meet the following criteria: - ALT >ULN but =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Pregnant or breast feeding women or women who believe they may wish to become pregnant during the course of the study or within 30 days or one menstrual cycle (whichever is longer) of last study drug administration • Males who have partners planning to become pregnant during the course of the study or within 90 days of the last dose of study drug. • Females and males of reproductive potential who are unwilling to use effective method(s) of birth control while enrolled in the study and for a minimum of 30 (or one menstrual cycle, whichever is longer) or 90 days, respectively, after ingestion of the last dose of study medication. • Infection with HCV genotype 3 • Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) or liver disease of non-HCV etiology • Presence of pancreatitis • History of solid organ transplantation • Presence of autoimmune disease • History of malignancy (history of localized squamous or non-invasive basal cell skin cancers successfully treated more than 5 years from screening is permitted) • Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males or binge drinking • History of seizure, including a single episode • Is a public transportation operator or operates heavy construction machinery • Recent significant infection • History of or current evidence of hepatocellular carcinoma (HCC; e.g., a-fetoprotein > 50 ng/mL or as indicated by recent imaging [ultrasound or triple-phase IV contrast CT/MRI] performed within 3 months prior to screening or, if recent imaging has not been performed, prescence of hepatic nodule on screening right upper quadrant [RUQ] ultrasound that is consistent with a diagnosis of HCC) • Decompensated liver disease, as indicated by total bilirubin > 1.5 x ULN, prothrombin time > 1.5 x ULN, platelets < 75,000/mm3 or albumin < 3 g/dL at screening OR current or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy or variceal hemorrhage) • Presence of Child-Pugh grade B or C cirrhosis • Hb < 10 g/dL at Screen •ANC < 1,000 cells/mm3 at Screen • Have initiated therapy with agents having potential hepatic anti-inflammatory or anti-fibrotic properties within 90 days prior to Baseline (Day 1) or are expected to initiate such therapy during the study. Such agents include (but are not limited to): angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, peroxisome proliferator-activated receptor agonists, ursodeoxycholic acid, mycophenolate, pentoxifylline. Subjects who have received such agents may be eligible if they have received stable therpay (including dose) for = 90 days prior to Baseline (Day 1) and are anticipated to continue therapy throughout the study; consultation with the GSI Medical Monitor is required prior to enrollment of such subjects • Have received treatment with silymarin (milk thistle) within 90 days prior to Baseline (day 1) or are expected to receive silymarin at anytime during the study. • Have initiated therapy with potentially hepatotoxic/cholestatic drugs within 90 days prior to Baseline or are expected to initiate such therapy during the study. Subjects who have received such agents may be eligible if they have received stable therapy (including dose) for at least 90 days prior to Baseline and are anticipated to continue therapy throughout the study. Intermittent use of acetaminophen in recommended doses is permitted • Are expected to receive
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of two oral doses of GS 9450 to placebo in subjects with chronic HCV infection as evidenced by histologic response (at least a 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score) at Week 24.;Secondary Objective: • To compare the safety and tolerability of two oral doses of GS 9450 to placebo in subjects with chronic HCV • To compare the efficacy of two oral doses of GS 9450 to placebo in subjects with chronic HCV, as evidenced by: — Change from baseline in the Knodell necroinflammatory score — Change from pretreatment in alanine aminotransferase (ALT) levels; — Change from pretreatment in aspartate aminotransferase (AST) levels; — Change from baseline in CK–18 caspase cleavage fragments; — Change from baseline in hepatic collagen content as measured by morphometry of liver biopsy specimens; — Evaluation of Ishak scoring relative to baseline; — Change from baseline in hepatic apoptosis as measured by TUNEL staining of liver biopsy specimens; and — Change from baseline in hepatic CK–18 neoantigen expression as measured by immunohistochemical staining of liver biopsy specimens ;Primary end point(s): Histologic response (at least 2 point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score) at Week 24. | — |
Countries
Germany, United Kingdom
Outcome results
None listed