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

Официальное название

Efficacy and Safety of HuHuangLianzonggan Capsule in Subjects With Nonalcoholic steatoHEPAtitis: a Randomized, Double-blind, Placebo-controlled, Multi-center, Phase 2 tRial(HHL-HEPAR)

Обзор

This study will evaluate the efficacy and safety and the best effective dose of HuHuangLianzonggan capsule in subjects with nonalcoholic steatohepatitis.

Вмешательства

• Препарат HuHuangLianzonggan capsule
  HuHuangLianzonggan capsule, 4 pills(120 mg per pill), take orally after meals, 2 times a day for 12weeks
• Препарат HuHuangLianzonggan capsule placebo
  HuHuangLianzonggan capsule placebo, 4 pills(120 mg per pill), take orally after meals, 2 times a day for 12weeks

Первичные конечные точки

• Change from baseline in hepatic fat fraction assessed by MRI-PDFF at week 12. [Срок оценки: Week 12]
• Proportion of subjects with ≥ 30% relative fat reduction on MRI-PDFF at week 12. [Срок оценки: Week 12]

Вторичные конечные точки (12)

• Change from baseline in weight at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in Body Mass Index (BMI) at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in waist hip rate at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in fasting blood glucose at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in 2 hours postprandial hyperglycemia at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in homeostasis model assessment-insulin resistance (HOMA-IR) at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in Total Cholestrol (TC) at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in triglyceride (TG) at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in Low Density Lipoprotein Cholesterol (LDL-C) at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in High Density Lipoprotein Cholesterol (HDL-C) at week 4, 12. [Срок оценки: Week 4, 12]
• Change from baseline in Glycosylated hemoglobin A1c (HbA1c) at week 12. [Срок оценки: Week 12]
• Change from baseline in Alanine aminotransferase (ALT) at week 4, 12. [Срок оценки: Week 4, 12]

Критерии участия

Критерии включения

• Males and females between 18-75 years of age inclusive(including boundary values).
• Must have had a liver biopsy proven NASH within 6 months or in screening test. The following two requirements must be met at the same time: ① a non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 4 with at least a score of 1 in each of the following NAS components: Steatosis≥1, Lobular inflammation≥1, Ballooning degeneration≥1;② fibrosis stage 1 to 3.
• Must have confirmation of ≥ 8% liver fat content on magnetic resonance imaging- proton density fat fraction (MRI-PDFF) at screening.
• No alcohol consumption or history of excessive alcohol consumption: less than 210 g of ethanol per week for men and 140 g for women in the past 12 months.
• Patients who are taking chronic drugs(including but not limited to antihypertensive drugs, antiatherogenic drugs, oral hypoglycemic drugs, insulin) need to have a steady dose for at least 3 months before liver biopsy.
• Weight was stable(the change is no more than 5%) during the 6 months prior to Screening.
• No attempt to change lifestyle (diet and/or exercise) during the 3 months prior to Screening.
• Ability to understand the requirements of the study and willingness to provide written informed consent.
• Have no pregnancy program and take effective contraceptive measures voluntarily.
• Abide by the experimental protocol and cooperate with the data collection according to the researcher's judgment.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 20 центров

• Anhui Provincial Hospital — Хэфэй
• The Second Hospital of Anhui Medical University — Хэфэй
• Peking University Third Hospital — Пекин
• The first affiliated hospital of Fujian medical university — Фучжоу
• Nanfang Hospital, Southern Medical University — Гуанчжоу
• The Third People's Hospital of Shenzhen — Шэньчжэнь
• The First Affiliated Hospital of Henan University of Science and Technology — Luoyang
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Ухань
• … и ещё 12 центров

Идентификаторы

NCT: NCT05632861 · TSL-TCM-HHLZGJN-NASH-Ⅱ

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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