Study of Aramchol in Patients With Fatty Liver Disease or Nonalcoholic Steatohepatitis

A Phase II, multicenter, double blind, randomized, placebo controlled study on the effect of Aramchol on liver triglycerides concentration in patients with steatosis due to NAFLD or NASH

The purpose of the study is to test whether Aramchol will reduce safely and effectively liver fat concentration in patients with NAFLD and NASH.

Aramchol inhibits the liver enzyme Stearoyl Coenzyme A Desaturase (SCD). It reduces fatty acid synthesis while increasing fatty acid oxidation. It was shown to reduce liver fat in animal models with diet induced Fatty Liver. It has also marked hypocholesterolemic effects, mainly via upregulation of theABCA1 cholesterol transporter. It thus causes(incomplete) SCD inhibition while being antiatherogenic

Primary purpose: Compare the changes in liver triglycerides concentration in the Aramchol versus the placebo arm following three month treatment.

Secondary purpose: Comparing liver enzymes, markers of endothelial dysfunction, insulin resistance, SCD1 activity and cholesterol synthesis and lipid levels, between the Aramchol and the placebo arms.

Inclusion criteria

• Patients with histologically proven NAFLD or NASH based on a biopsy performed during the preceding 18 months fulfilling the following criteria:

• At least 15% of hepatocytes showing steatosis,with Fibrosis of not more than stage 3, with at most bridging fibrosis.

Patients with a NAFLD activity score 0-2 will be considered to have NAFLD. Biopsies with an activity score of 3 or more will be considered NASH.

• Triglycerides concentration in the liver of 6% or more as measured by NMRS.
• At least two elevated serum ALT levels in the previous six months, with latest test within 2 months of trial.
• Normal or only slightly impaired synthetic liver function (serum albumin >3.5gm%, INR 0.8-1.3)
• Male or female aged 18-75 years.
• Negative pregnancy test at study entry for females of child bearing potential.
• Females of child bearing potential practicing reliable contraception throughout the study period.
• Signature of the written informed consent

Exclusion criteria

• Evidence of cirrhosis on liver biopsy.
• Evidence of fibrosis of more than stage 3 on liver biopsy.
• Patient with liver disease due to acute or chronic hepatitis A, B,C, HIV, and all other liver diseases affecting liver function. Patients with cysts, hemangiomas, or similar abnormalities, are accepted.
• BMI > 35 or >130 kg body weight
• Any other concomitant, significant: metabolic, infectious, inflammatory, neoplastic, or other non-liver disease.
• Various concomitant diseases requiring chronic steroid administration.
• Use of warfarin, metformin, thiaglitazones, insulin or current steroid therapy of more than 3 days.
• Use of other investigational agents < 30 days prior to the study.
• Pregnancy
• Daily alcohol intake > 10gm/day.
• Patients with symptoms of significant mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent.
• Performance status: WHO performance status ≥4.