A study to investigate the efficacy and safety of Aramchol in patients with a form of fatty liver disease.

Phase 1

Conditions: onalcoholic Steatohepatitis (NASH)
MedDRA version: 22.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2019-002073-56-ES

Lead Sponsor: Galmed Research and Development, Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2000

Inclusion Criteria

1. Male or female age 18 to 75 years (inclusive at first Screening visit)
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
5. Subjects who have had a biopsy more than 3 months before
randomization should have stable weights between the time of the
biopsy and screening. Stable weight is defined as no more than a 5
percent change
6. Body mass index (BMI) between 25kg/m2 and 40 kg/m2
7. AST>20 IU/L
8. Type 2 diabetes mellitus or prediabetes: Type 2 diabetes diagnosis must be established and documented prior to screening. For prediabetes, the diagnosis should be based on screening results (by central lab) according to the American Diabetes Association criteria, which requires at least one of the following 3 criteria:
• Fasting Plasma Glucose > 100mg/dL (5.5 mmol/L)
• Post-load glucose (2hPG) following 75g oral glucose tolerance test (OGTT) > 140 mg/dL (7.8 mmol/L)
• Glycosylated Hemoglobin (HbA1c) > 5.7%
9. For subjects with type 2 diabetes, glycemia must be controlled (HbA1c = 9%)
10. Negative blood pregnancy test at study entry for females of childbearing potential confirmed by central laboratory
11. Females of childbearing potential must practice a highly effective
method of contraception throughout the study period and for 1 month after treatment discontinuation. Highly effective methods are defined as those that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods, in accordance with the recommendations of the Clinical Trial Facilitation Group (CTFG) Working Group on Contraception include: Hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence
12. Able to understand the nature of the study and to provide signature of the written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 500

Exclusion Criteria

1. Histologically documented liver cirrhosis (fibrosis stage 4)
2. Inability or unwillingness to undergo a liver biopsy
3. Abnormal synthetic liver function
• Albumin below the lower limit of the normal range
• International Normalized Ratio (INR) = 1.3; unless related to use of
anticoagulants
• Total bilirubin = 1.3 mg/dL (22.2 µmol/L); patients with a documented history of Gilbert’s syndrome can be enrolled if the direct bilirubin is within normal reference range
4. ALT or AST >5× upper limit of normal (ULN); according to central
laboratory
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 unless related to anticoagulant use
9. Prior history of/or planned liver transplantation
10. Prior history or presence of decompensated liver disease
11. Evidence of portal hypertension (e.g., low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly)
12. Other (acute or chronic) coexisting liver disease based on medical history and/or centralized review of liver histology (e.g. viral hepatitis, unless eradicated at least 3 years prior to screening; Primary biliary cholangitis (PBC); Primary sclerosing cholangitis (PSC); genetic hemochromatosis; Wilson disease; alpha 1 antitrypsin deficiency; autoimmune hepatitis; alcoholic liver disease; drug-induced liver disease)
13. Known alcohol and/or any other drug abuse or dependence in the last five years
• Daily alcohol intake will be an exclusion if >20 g/day for women and
>30 g/day for men (on average per day), as per medical history
14. Human immunodeficiency virus HIV infection (either known or diagnosed during Screening blood tests)
15. Known familial (i.e., genetic) hypertriglyceridemia and familial (i.e., genetic) hypercholesterolemia
16. Diabetes Mellitus other than type 2 (type 1, endocrinopathy, genetic syndromes etc.)
17. Weight loss of more than 5% within 3 months prior to screening
18. History of bariatric surgery within 5 years of liver biopsy or planned surgery for weight reduction
19. Treatment with drugs that may cause NAFLD within 12 months prior to liver biopsy (e.g. valproic acid, tamoxifen, methotrexate, amiodarone, chronic treatment with corticosteroids, high dose estrogen and tetracycline)
20. Treatment with Vitamin E unless started at least 12 months prior to biopsy, with stable dose in the 6 months prior to biopsy
• Subjects that stopped treatment less than 6 months prior to biopsy
should be excluded
21. Treatment with GLP-1 receptor agonists or thiazolidinediones (TZDs) unless started at least 12 months prior to biopsy, with stable dose in the 6 months prior to biopsy
• Subjects that stopped treatment less than 6 months prior to biopsy
should be excluded
22. Treatment with SGLT-2 inhibitors, metformin, sulfonylurea, insulin, and DPP-4 inhibitors unless the prescribed dose has been stable for 3 months prior to screening
23. Treatment with fibrates and statins unless the prescribed dose has been stable for 3 months prior to screening
24. Previous treatment with polyunsaturated fatty acid, ursodeoxycholic acid or fish oil unless stable for at least 6 months prior to screening or stopped at least 3 months prior to screening
25. Current or planned treatment with immunosuppressive drugs (e.g. adalimumab, azathioprine and methotrexate)
26. Evidence of any other unstable or untreated clinically significant hepatic, cardiovascular

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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