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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Placebo Controlled Randomised Study of Aramchol on Liver Triglyceride in Patients With Steatosis Due to NAFLD or NASH

Conditions
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Non-Alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Metabolic Syndrome

Intervention / Treatment
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* Drug: Aramchol
* Drug: Aramchol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high dose<br>Aramchol 300 mg daily (high dose) | Drug: Aramchol<br>* 300 mg/d tablets packaged in bottles given orally once a day in the morning within 10 minutes after breakfast for a total period time of 3 months<br>* Other names: Arachidyl amido cholanoic acid;|
| Experimental: low dose<br>100 mg daily (low dose) | Drug: Aramchol<br>* 100mg/d tablets packaged in bottles given orally once a day in the morning within 10 minutes after breakfast for a total period time of 3 months<br>* Other names: Arachidyl amido cholanoic acid;|
| Placebo Comparator: Placebo<br>Placebo and two doses will be compared. The Aramchol: placebo ratio is of 2:1. | Drug: Placebo<br>* tablets packaged in bottles given orally once a day in the morning within approximately 10 minutes after breakfast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference between initial and final liver triglyceride concentration (measured by NMRS) comparing the Aramchol and placebo treated patients. |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing secondary variables of liver, metabolic and endothelial functions between the Aramchol and the placebo arms. | Comparing liver enzymes, markers of endothelial dysfunction, insulin resistance, SCD1 activity and cholesterol synthesis and lipid levels, between the Aramchol and the placebo arms | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, NASH, Fatty Liver, Metabolic Syndrome, Endothelial Dysfunction, Insulin Resistance, Liver Fat