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

NASH Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05632861
• Other study ID #: TSL-TCM-HHLZGJN-NASH-?
• Status: Recruiting
• Phase: Phase 2
• Start date: February 21, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: Tasly Pharmaceutical Group Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Males and females between 18-75 years of age inclusive(including boundary values).

2. 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: ? 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;? fibrosis stage 1 to 3.

3. Must have confirmation of = 8% liver fat content on magnetic resonance imaging- proton density fat fraction (MRI-PDFF) at screening.

4. 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.

5. 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.

6. Weight was stable(the change is no more than 5%) during the 6 months prior to Screening.

7. No attempt to change lifestyle (diet and/or exercise) during the 3 months prior to Screening.

8. Ability to understand the requirements of the study and willingness to provide written informed consent.

9. Have no pregnancy program and take effective contraceptive measures voluntarily.

10. Abide by the experimental protocol and cooperate with the data collection according to the researcher's judgment.

Exclusion Criteria:

1. 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]).

2. 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.

3. Model for End-stage Liver Disease (MELD) score >12.

4. Histologically documented liver cirrhosis (fibrosis stage F4), history or current diagnosis of hepatocellular carcinoma HCC.

5. History of or planned liver transplant.

6. Viral hepatitis:Positive hepatitis A antibody,Positive hepatitis D antibody,Positive hepatitis E antibody,Positive hepatitis B surface antigen (HBsAg) ,Positive hepatitis C antibody.

7. 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).

8. In patients who are not anticoagulated, INR = 1.3 times ULN or other evidence of impaired coagulation.

9. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value <30 mL/min/1.73 m2.

10. Patient currently receiving any approved treatment for NASH.

11. HbA1c =9% or fasting blood-glucose>13.9 mmol/L at Screening.

12. Diabetes mellitus other than type 2 (e.g. type 1, diabetes caused by drugs or chemicals, and immune-mediated diabetes).

13. Those who are underweight, of normal weight, or severely obese, i.e BMI<23 kg/m2 or BMI=40 kg/m2.

14. Bariatric surgery or tumor surgery are not allowed within 5 years of the qualifying liver biopsy.

15. Uncontrolled hypertension (values =160/100 mm Hg) or hypotension(values <80/50 mmHg).

16. Acute vascular events including ACS, stroke, peripheral vascular disease worsened, or any vascular/cardiac surgery within the 6 months prior to Screening.

17. Concomitant mental illness and poor condition control, which affects the signing of informed consent or presentation of adverse events.

18. Do not have a liver biopsy within the 6 months prior to Screening and refuse to take liver biopsy at Screening.

19. Allergic constitution, or allergic to the test drug or its ingredients.

20. Women who are pregnant or lactating.

21. Participate in clinical trials of other drugs within 3 months before screening.

22. The researchers did not consider it appropriate to participate in this study.

Related Conditions & MeSH terms

• Fatty Liver
• NASH
• Non-alcoholic Fatty Liver Disease

Intervention

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

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing	Beijing
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	The first affiliated hospital of Fujian medical university	Fuzhou	Fujian
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	The First People's Hospital of Lianyungang	Lianyungang	Jiangsu
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	The Affiliated Hospital of Nanjing University medical school,Nanjing Drum Tower Hospital	Nanjing	Jiangsu
China	The Second Hospital of Nanjing	Nanjing	Jiangsu
China	Ningbo Huamei Hospital, University of Chinese Academy of Sciences	Ningbo	Zhejiang
China	Ningbo Medical Center Lihuili Hospital	Ningbo	Zhejiang
China	The Third People's Hospital of Shenzhen	Shenzhen	Guangdong
China	Taizhou Municipal Hospital	Taizhou	Zhejiang
China	Tianjin Second People's Hospital	Tianjin	Tianjin
China	Rui'an People's Hospital	Wenzhou	Zhejiang
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia

Sponsors (1)

Lead Sponsor	Collaborator
Tasly Pharmaceutical Group Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in hepatic fat fraction assessed by MRI-PDFF at week 12.		Week 12
Primary	Proportion of subjects with = 30% relative fat reduction on MRI-PDFF at week 12.		Week 12
Secondary	Change from baseline in weight at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Body Mass Index (BMI) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in waist hip rate at week 4, 12.		Week 4, 12
Secondary	Change from baseline in fasting blood glucose at week 4, 12.		Week 4, 12
Secondary	Change from baseline in 2 hours postprandial hyperglycemia at week 4, 12.		Week 4, 12
Secondary	Change from baseline in homeostasis model assessment-insulin resistance (HOMA-IR) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Total Cholestrol (TC) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in triglyceride (TG) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Low Density Lipoprotein Cholesterol (LDL-C) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in High Density Lipoprotein Cholesterol (HDL-C) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Glycosylated hemoglobin A1c (HbA1c) at week 12.		Week 12
Secondary	Change from baseline in Alanine aminotransferase (ALT) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Aspartate aminotransferase (AST) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in total bilirubin (TBil) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Cytokeratin18 (CK-18) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in N-terminal type ? collagen propeptide (Pro-C3) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Fibrosis 4 score at week 4, 12.		Week 4, 12
Secondary	Change from baseline in Chronic Liver Disease-NAFLD questionnaire (CLDQ-NAFLD) at week 4, 12.		Week 4, 12
Secondary	Change from baseline in ferritin at week 4, 12.		Week 4, 12