A placebo-controlled clinical trial to evaluate the efficacy and safety of two Aramchol doses in patients with Non-Alcoholic- Steatohepatitis (NASH).

Phase 1

Active, not recruiting

• Conditions: on-alcoholic Steatohepatitis in patients with two additional features of metabolic syndrome -overweight or obesity and Diabetes Mellitus type II or pre-diabetes.; MedDRA version: 19.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-003107-29-LT
• Lead Sponsor: GALMED Pharmaceuticals LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-31
• Last Update Posted: 2018-08-20

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Male or female age 18 to 75 years.
2. 25 = BMI =40 kg/m2 or waist circumference > 88 <200 cm for women and > 102 <200 cm for men.
3. Known type II Diabetes Mellitus or pre-Diabetes according to American Diabetes Association. One of the following 3 criteria is needed for pre-Diabetic: Fasting Plasma Glucose > 100mg/dl (5.5 mmol/l) or 2hPG following 75g OGTT > 140 (7.8 mmol/l) mg/dl or HbA1c > 5.7%.
4. Histologically proven Steatohepatitis on a diagnostic liver biopsy performed within 6 months before screening visit, confirmed by central laboratory reading of the slides (steatosis > 5% + lobular inflammation, any ballooning, any amount).
5. Liver fat concentration of 5.5% or more as measured by NMRS.
6. Biopsies with an activity NAS score of 4 or more.
7. Normal synthetic liver function (serum albumin >3.5g/l, INR 0.8-1.3).
8. Understanding the nature of the study and signature of the written informed consent.
9. Negative pregnancy test at study entry for females of child bearing potential.
10. Females of child bearing potential practicing reliable contraception throughout the study period (including oral contraceptives). If barrier methods are used, it is recommended to practice two methods (e.g. male condom + female diaphragm with spermicide). For country-specific requirements (e.g. Germany) contraception failure rates (Pearl Index) should be under 1% in accordance with the recommendations of the CTFG Working Group on Contraception.
11. Hypertensive patients must be well controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study).
12. Patients previously treated with vitamin E (>400IU/day), Polyunsaturated fatty acid (>2g/day), Ursodeoxycholic acid or fish oil can be included if drugs are stopped at least 3 months prior to diagnostic liver biopsy and up to the end of study unless on stable dose for the last 12 months prior to biopsy.
13. For patients with type II Diabetes, glycaemia must be controlled (Glycosylated Hemoglobin A1c = 9% while any HbA1c change should not exceed 1.5% during the 6 months prior to enrollment). Treatments with metformin, sulfonylurea and insulin are authorized. sulfonylurea and insulin are permitted if glycaemia is self-monitored by the patient.
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1. Patients with other active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, genetic hemochromatosis, Wilson disease, alpha 1antitripsin deficiency, alcohol liver disease, drug induced liver disease) at the time of randomization.
2. Patients who have liver cirrhosis (CRN fibrosis score =4).
3. Known Alcohol and/or any other drug abuse or dependence in the last five years.
4. Known history or presence of clinically significant cardiovascular, hepatic other than NASH, gastrointestinal, metabolic other than Diabetes Mellitus, neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder or nephrotic syndrome.
5. Patients with familial hypertriglyceridemia and familial hypercholesterolemia.
6. History or presence of any disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs including bile salt metabolism (e.g. inflammatory bowel disease (IDB); previous intestinal (ileal or colonic) operation; chronic pancreatic; celiac disease or previous vagotomy.
7. Patients with heart or brain pacemaker.
8. History of surgery within three months of screening which involved stent transplant or any other surgery which includes transplantation of metal devices (e.g. knee, hip etc.)
9. Weight loss of more than 5% within 6 months prior to randomization.
10. History of bariatric surgery within 5 years of liver biopsy.
11. Uncontrolled blood pressure.
12. Women who are pregnant or breast feeding.
13. Diabetes Mellitus other than type II (type I, endocrinopathy, genetic syndromes etc.).
14. Patients with HIV infection.
15. Daily alcohol intake >20 g/day for women and >30 g/day for men (on average per day), as per medical history.
16. Treatment with other anti-diabetic medications: DPP-4 inhibitors unless it was stopped 6 months before biopsy,GLP-1 receptor agonists (such as Januvia [Sitagliptin], Byetta [Incretin], etc.) unless it was started at least 12 months and on stable dose over 6 months prior biopsy is taken. In case GLP-1 receptor agonist being stopped, it should be at least 6 months prior to biopsy, as per medical history.
17. Metformin, fibrates, statins, insulin, sulfonylurea unless the dose has been stabilized for the last 6 months prior to the screening visit.
18. Treatment with Valproic acid, Tamoxifen, Methotraxete, Amiodarone or chronic treatment with anti-cholinergic agents within 12 months prior to the screening visit.
19. Chronic antibiotic treatment (e.g. Rifaximin).
20. Homeopathic and/or alternative treatments. Any treatment should be stopped during the screening period, at least 48 hours before randomization.
21. Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone >2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted.
22. Patients with renal dysfunction eGFR< 40.
23. Unexplained serum creatine phosphokinase (CPK) >3X the upper limit of normal (ULN). Patients with an intermittent CPK elevation may have the repeated measurement prior to randomization; a CPK retest > 3X ULN leads to exclusion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified