HuHuangLianzonggan Capsule in Subjects With Nonalcoholic Steatohepatitis: a Phase 2 tRial(HHL-HEPAR)

Exclusion Criteria22

• Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy (e.g. valproic acid, tamoxifen, methotrexate, amiodarone, oral corticosteroids, >5 mg/day of prednisone equivalent \[one short (<2 weeks) course of oral corticosteroids, more than 3 months before the liver biopsy is allowed\], or oestrogens \[at doses greater than those used for contraception or hormone replacement\]).
• Documented causes of fatty liver disease other than NASH including, but not restricted to: HCV-associated fatty liver (genotype 3), hepatolenticular degeneration, autoimmune hepatitis, total parenteral nutrition, abetalipoproteinemia, lipoatrophy , Coeliac disease, Primary sclerosing cholangitis, Alpha-1-antitrypsin deficiency, Drug-induced liver disease.
• Model for End-stage Liver Disease (MELD) score >12.
• Histologically documented liver cirrhosis (fibrosis stage F4), history or current diagnosis of hepatocellular carcinoma HCC.
• History of or planned liver transplant.
• Viral hepatitis：Positive hepatitis A antibody，Positive hepatitis D antibody，Positive hepatitis E antibody，Positive hepatitis B surface antigen (HBsAg) ，Positive hepatitis C antibody.
• Abnormal liver function as defined by Screening central laboratory evaluation of any of the following: ALT or AST >5 × ULN; Alkaline phosphatase (ALP) >2 × ULN; albumin below the lower limit of the normal range; total bilirubin level >1.5 × ULN (patients with a documented history of Gilbert's syndrome can be enrolled if the direct bilirubin is within normal reference range).
• In patients who are not anticoagulated, INR ≥ 1.3 times ULN or other evidence of impaired coagulation.
• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value <30 mL/min/1.73 m2.
• Patient currently receiving any approved treatment for NASH.
• HbA1c ≥9% or fasting blood-glucose>13.9 mmol/L at Screening.
• Diabetes mellitus other than type 2 (e.g. type 1, diabetes caused by drugs or chemicals, and immune-mediated diabetes).
• Those who are underweight, of normal weight, or severely obese, i.e BMI<23 kg/m2 or BMI≥40 kg/m2.
• Bariatric surgery or tumor surgery are not allowed within 5 years of the qualifying liver biopsy.
• Uncontrolled hypertension (values ≥160/100 mm Hg) or hypotension（values <80/50 mmHg）.
• Acute vascular events including ACS, stroke, peripheral vascular disease worsened, or any vascular/cardiac surgery within the 6 months prior to Screening.
• Concomitant mental illness and poor condition control, which affects the signing of informed consent or presentation of adverse events.
• Do not have a liver biopsy within the 6 months prior to Screening and refuse to take liver biopsy at Screening.
• Allergic constitution, or allergic to the test drug or its ingredients.
• Women who are pregnant or lactating.
• Participate in clinical trials of other drugs within 3 months before screening.
• The researchers did not consider it appropriate to participate in this study.