A study to investigate the efficacy and safety of Aramchol in patients with a form of fatty liver disease.
- Conditions
- onalcoholic Steatohepatitis (NASH)MedDRA version: 22.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2019-002073-56-BE
- Lead Sponsor
- Galmed Research and Development, Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 2000
The inclusion criteria for the Open-Label Part are the same as those of the Randomized, Double-Blind, Placebo-Controlled Part with the
exception of fibrosis stage (the Open-Label Part allows enrollment of subjects with fibrosis stage 1), weight (the Open-Label Part allows
enrollment of subjects who are not overweight) and Type diabetes mellitus (the Open-Label Part allows enrollment of subjects who are not prediabetic or subjects who do not have type 2 diabetes mellitus).
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
• Open-Label Part: biopsy obtained within 9 months prior to randomization or during the screening period.
• Randomized, Double-Blind, Placebo-Controlled Part: 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 only: 30 subjects with fibrosis stage 1 may be included
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)
• Open-Label Part: = 40 kg/m2
• Randomized, Double-Blind, Placebo-Controlled Part: between 25kg/m2 and 40 kg/m2
7. The subject made at least one attempt of dietary and/or lifestyle change guided by professional counseling in the past and no new attempts to make dietary and/or lifestyle changes have been initiated within the 3 months prior to screening or is actively being sought now
8. Randomized, Double-Blind, Placebo-Controlled Part only: Type 2 diabetes mellitus or prediabetes: Type 2 diabetes diagnosis must be established and documented prior to screening. For prediabetes, unless pharmacologically treated, the diagnosis should be verified by 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 100 - 125 mg/dL (5.6 - 6.9 mmol/L)
• Post-load glucose (2hPG) following 75g oral glucose tolerance test
(OGTT) 140 - 199 mg/dL (7.8 -11.0 mmol/L)
• Glycosylated Hemoglobin (HbA1c) 5.7% - 6.4%
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 at least 1 month prior to randomization, throughout the study period and for 1 month after treatment discontinuation
- A woman is considered of childbearing potential if fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
- 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, intr
All exclusion criteria for the Open-Label Part are the same as those of the Randomized, Double-Blind, Placebo-Controlled Part.
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;
• Total bilirubin = 1.3 mg/dL (22.2 µmol/L); subjects 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 using OPTN formula
9. Prior history of/or planned liver transplantation
10. Prior history or presence of decompensated liver disease
11. Current or past 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 including:
• Subjects positive for hepatitis C antibodies unless sustained virologic response (SVR) is documented at least 3 years prior to screening and
confirmed at screening by central laboratory
• Subjects positive for Hepatitis B surface antigen (HBsAg)
• Primary biliary cholangitis (PBC)
• Primary sclerosing cholangitis (PSC)
• Genetic hemochromatosis
• Wilson's 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 or 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 the 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 month
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