Clinical Trials

Inclusion Criteria:

• Adult subjects aged between 18-75
• Histological evidence of NASH, based on biopsy, with a NAS of >= 4 with at least 1 in each component of NAS
• Histological evidence of liver fibrosis defined as NASH CRN System Stage 1 to 3
• Meeting any of the 3 major criteria (a, b, c):
  1. Documented evidence of type 2 diabetes mellitus
  2. High body mass index (> 25 kg/m2) with at least one of the following criteria of metabolic syndrome, as defined by the National Cholesterol Education Program:
     • Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches (female)
     • Dyslipidemia: Triglycerides ≥ 1.7 mmol/L (150 mg/dL)
     • Dyslipidemia: High-density lipoprotein (HDL)-cholesterol < 40 mg/dL (male), < 50 mg/dL (female)
     • Blood pressure ≥ 130/85 mmHg (or currently being treated for hypertension)
     • Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dL)
  3. Bridging fibrosis (NASH CRN Stage 3) and/or definite NASH (NAS ≥ 5)
• Agree to have one liver biopsy at Screening, one at Year 1, and one at the end of study treatment (Year 2)
• AST and ALT ≤ 5 × upper limit of normal (ULN)

Exclusion Criteria:

• Hepatitis B surface Antigen (HBsAg) positive
• Hepatitis C antibody (HCVAb) positive with the following 2 exceptions:
  1. Subjects previously treated for viral hepatitis C with at least a 1-year period since documented sustained virologic response at Week 12 (post-treatment) may be eligible if all other eligibility criteria are met
  2. Subjects with presence of hepatitis C antibody but negative hepatitis C virus RNA without treatment (i.e., spontaneous clearance) may be eligible if all other eligibility criteria are met
• Prior or planned liver transplantation
• Other known causes of chronic liver disease, including alcoholic liver disease
• History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding
• Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is ½ pint of beer [285 mL], 1 glass of spirits [25 mL] or 1 glass of wine [125 mL])
• HIV-1 or HIV-2 infection
• Weight reduction through bariatric surgery in the past 5 years or planned during the conduct of the study (including gastric banding)
• Females who are pregnant or breastfeeding
• Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements.