A Clinical Study to Evaluate the Efficacy and Safety of Aramchol in Subjects With NASH (ARMOR)

An Open-Label Part was added:

This part will enroll in selected sites which are less affected by the COVID-19 pandemic.

150 subjects with NASH and fibrosis confirmed by liver histology (F1-F3) will be randomized into 3 groups according to the post-baseline biopsy.

The objective of the Open-Label Part is:

* To evaluate the safety and PK of twice daily administration (BID) of Aramchol 300mg in subjects with NASH and liver fibrosis.
* To explore the kinetics of histological outcome measures and Non-Invasive Tests (NITs) associated with NASH and fibrosis for the treatment duration of 24, 48 and 72 weeks.

All patients will be allocated to Aramchol.

Double Blind Part:

This part is double blind, placebo controlled randomized in subjects with NASH and fibrosis stages 2-3 who are overweight or obese and have prediabetes or type 2 diabetes.

The primary objectives of this part of the study are to evaluate the effect of Aramchol as compared to placebo on NASH resolution, fibrosis improvement and clinical outcomes related to progression of liver disease.

Subjects will be randomized to receive Aramchol 300mg BID or matching placebo in a 2:1 randomization ratio.

This double-blind phase of the study will recruit patients once the study will be continued.

A total of 150 subjects, including those already randomized to Aramchol 300 mg BID or Placebo, were to be randomized in a ratio of 1:1:1 to receive Aramchol 300 mg BID in the open-label (OL) part according to the grouping below:

Group A: The post-baseline liver biopsy was to be conducted at Week 24 Group B: The post-baseline liver biopsy was to be conducted at Week 48 Group C: The post-baseline liver biopsy was to be conducted at Week 72

In order to more comprehensively explore the kinetics of histological outcome measures (e.g., are there subjects who did not show improvement in outcome at Weeks 24, 48, or 72, but improved with longer duration of treatment), a second post-baseline liver biopsy sample was to be collected for subjects whose post-baseline liver biopsy at Weeks 24 or 48, or 72 did not show at least one stage improvement in fibrosis (fibrosis non-responders). The second post-baseline liver biopsy sample was to be collected one year later (i.e., at Weeks 72 or 96 or 120, respectively).

Subjects already randomized and ongoing in the PC part were given the option to switch to the OL part

Eligibility Criteria:
Key Inclusion Criteria:

1. Male or female age 18 to 75 years
2. Histological confirmation of NASH on a diagnostic liver biopsy by central reading of the slides (biopsy obtained within 6 months prior to randomization or during the screening period)
3. Total NAS Score 4 or more with at least 1 in each component of the NAS Score (steatosis ≥1 AND inflammation ≥1 AND ballooning ≥1)
4. Fibrosis Stage must be 2 or 3 (Open-Label Part may include up to 30 subjects with fibrosis stage 1)
5. Body mass index (BMI) between 25kg/m2 and 40 kg/m2 (Open Label part: BMI \<40 kg/m2)
6. AST\>20 IU/L
7. Type 2 diabetes mellitus or prediabetes (Open Label Part only: Type 2 diabetes or prediabetes is not an inclusion criteria)
8. For subjects with type 2 diabetes, glycemia must be controlled
9. Females of childbearing potential must practice a highly effective method of contraception throughout the study period and for 1 month after treatment discontinuation.
10. Able to understand the nature of the study and to provide signature of the written informed consent.

Key Exclusion Criteria:

1. Histologically documented liver cirrhosis (fibrosis stage 4)
2. Inability or unwillingness to undergo a liver biopsy
3. Abnormal synthetic liver function
4. ALT or AST \>5× upper limit of normal (ULN)
5. Platelet count \< 150,000mm3
6. Alkaline phosphatase ≥2× ULN
7. Known or suspected hepatocellular carcinoma (HCC)
8. Model for End-Stage Liver Disease (MELD) score \> 12
9. Prior history or presence of decompensated liver disease
10. Other (acute or chronic) coexisting liver disease based on medical history and/or centralized review of liver histology)
11. Known alcohol and/or any other drug abuse or dependence in the last five years
12. Weight loss of more than 5% within 3 months prior to screening
13. History of bariatric surgery within 5 years of liver biopsy or planned surgery for weight reduction
14. Treatment with drugs that may cause NAFLD within 12 months prior to liver biopsy
15. Treatment with some anti-diabetic medications; Unless started prior to biopsy (timeframe depending on drug) and stable
16. Current or planned treatment with immunosuppressive drugs
17. Evidence of any other unstable or untreated clinically significant disease
18. Uncontrolled hypertension
19. Any other condition that in the opinion of the Investigator warrants exclusion from the study