A Phase II, Randomized, Double Blind, Placebo-Controlled Clinical Trial to Investigate the Anti-oxidant Activity of Heptex in Patients with Apparent Risk Factors of Nonalcoholic Steatohepatitis (NASH)

This is a phase II, randomized, double blind placebo-controlled, three-arm, parallel-group, intervention clinical trial evaluating anti-oxidant activity of Heptex; a herbal medicinal product of Aerial Parts of Phyllanthus niruri (Dukung Anak) and Fruits of Silybum marianum (Milk Thistle) in patients with apparent risk factors of NASH.

Inclusion Criteria:

1. Male or female aged between 18 and 65 years.

2. Both male and female patients who have childbearing potential must agree to practice an acceptable method of birth control during the study and for at least 6 months after the cessation of treatment; such contraceptive methods must include at least one barrier method.

3. Controlled Attenuation Parameter (CAP)-confirmed hepatic steatosis.

4. Patients with elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels but less than 2.5 times the upper limit of the normal range.

5. Liver fibrosis stage F1-F2 as diagnosed by the FibroScan liver stiffness measurement of 5-10 kPa.

6. Liver condition according the following criteria;

   • Serum albumin > 3 g/dl
   • INR < 2
   • No ascites on ultrasound
   • No documented or suspected hepatic encephalopathy

7. Willing to stop any other liver support and hepatoprotective medications throughout study duration.

8. Able and willing to provide written informed consent.

9. Able and willing to complete all study visits and procedures, including compliance with the requirements and restrictions listed in the consentform.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with BMI > 40 Kg/m2 or BMI < 18.5 Kg/m2.
3. Serum creatinine > 1.5 x ULN OR creatinine clearance (GFR) < 60 mL/minute.
4. Platelet count < 75,000/mm3.
5. Uncontrolled diabetes mellitus as evident by HbA1c ≥ 8.5%.
6. Patients who are currently receiving Thiazolidinediones.
7. Patients with ischemic heart disease (IHD).
8. History of parenteral nutrition.
9. History of liver transplant.
10. Viral hepatitis, drug-induced liver injury, metabolic liver disease or auto-immune liver disease.
11. Liver cancer or serum alpha-fetoprotein (AFP) >100ng/ml. Patients with an AFP between 50 and 100ng/ml may be included as long as a liver ultrasound within 3 months of screening, or at screening, shows no evidence of potential hepatocellular cancer.
12. Use of drugs known to induce steatosis (valproate, amiodarone or prednisone) or to affect body weight and carbohydrate metabolism.
13. Use of drugs known to alter liver enzymes.
14. Allergy or allergic history to any of the drug components.
15. History of alcohol abuse as assessed by the investigator within the past 2 years, or an alcohol use pattern that may interfere with the patient's study compliance. Patients must have abstained from alcohol for at least 6 months prior to study start.
16. Patients with history of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol.
17. Receipt of an investigational drug within 6 months prior to screening, or active enrolment in another investigational medication or device trial.
18. Patients with any chronic illness or prior treatment which in the opinion of the investigator should preclude participation in the trial.
19. Inability to understand and cooperate with the investigators or to give valid consent.

Double blinded