A Phase IIIc Clinical Study to Evaluate the Long-term Treatment of Hydronidone Capsules for Liver Fibrosis in Patients With Chronic Hepatitis B.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase IIIc Clinical Study Evaluating the Long-term Treatment of Hepatic Fibrosis in Chronic Hepatitis B With Hydronidone Capsules.

This study is conducted as a randomized, double-blind, placebo-controlled, multicenter clinical trial on a background of entecavir therapy. It aims to evaluate the clinical benefits of Hydronidone Capsules in patients with liver fibrosis due to chronic hepatitis B. The study consists of a Screening/Baseline Period (4 weeks) and a Dosing/Observation Period (planned duration of 5 years, including a 52-week primary treatment phase and a 208-week long-term treatment phase).

Inclusion Criteria:

• Age 18 to 65 years (inclusive of 18 and 65 years old at the time of signing the informed consent form), male or female;

• Documented history of chronic hepatitis B and/or positive for hepatitis B surface antigen (HBsAg) for ≥6 months;

• Treatment-naïve or treatment-experienced patients with chronic hepatitis B, defined as follows:

  1. Treatment-naïve patients must meet all of the following criteria:

     • No prior systemic antiviral therapy (e.g., interferon and/or nucleos(t)ide analogues) before randomization;
     • Positive for HBV DNA;
     • Liver stiffness measurement (LSM) by transient elastography ≥12.4 kPa for treatment-naïve patients with ALT >2 × ULN; or LSM ≥10.6 kPa for treatment-naïve patients with ALT ≤2 × ULN. Subjects whose LSM does not meet the above criteria may still be enrolled if they have liver biopsy evidence (within the past 6 months) confirming liver fibrosis of Ishak score ≥3.

  2. Treatment-experienced patients must meet all of the following criteria:

     • A history of ≥6 months of continuous nucleos(t)ide analogue therapy for hepatitis B up to randomization, currently receiving monotherapy with a nucleos(t)ide analogue [e.g., Tenofovir Alafenamide Fumarate (TAF), Tenofovir Disoproxil Fumarate (TDF), or Entecavir (ETV)];
     • HBV DNA positive or negative is acceptable;
     • Liver stiffness measurement (LSM) by transient elastography >9.0 kPa. Subjects whose LSM does not meet the above criteria may still be enrolled if they have liver biopsy evidence (within the past 6 months) confirming liver fibrosis of Ishak score ≥3.

• ALT <8 × ULN;

• No use within 3 months prior to randomization of the following Chinese patent medicines that may have antifibrotic effects: Fuzhenghuayu Capsule (Tablet), Anluohuaxian Pill, Compound Biejia Ruangan Tablet, etc.;

• Subjects (or their sexual partners) have no pregnancy plan during the trial and for 6 months after trial completion, voluntarily agree to use effective physical contraceptive methods, and have no plan to donate sperm or eggs;

• Subjects have fully understood the nature, significance, potential benefits, possible inconveniences, and potential risks of the trial prior to participation, voluntarily agree to take part in this clinical trial, are able to communicate well with the investigators, agree to comply with all study requirements, and have provided written informed consent.

Exclusion Criteria:

• Total bilirubin (TBil) >3 × ULN, or 3 × ULN < ALT <8 × ULN with TBil >2 × ULN;
• Platelet count (PLT) ≤50 × 10⁹/L;
• Prothrombin activity (PTA) <50% or International Normalized Ratio (INR) >1.5;
• Imaging findings suggestive of a space-occupying lesion in the liver indicative of tumor, or alpha-fetoprotein (AFP) >100 μg/L even in the absence of specific signs of hepatocellular carcinoma;
• Patients with decompensated liver cirrhosis (complications including ascites, esophageal and/or gastric variceal bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatopulmonary syndrome, hepatic encephalopathy, portal vein thrombosis, and cirrhotic cardiomyopathy) or with hepatic malignancy;
• Patients with chronic hepatitis C or non-viral chronic hepatitis (alcoholic, drug-induced, etc., excluding metabolic dysfunction-associated steatotic liver disease (MASLD));
• History of alcohol abuse or inability to abstain from alcohol recently [Note: Alcohol abuse is defined as: ① daily ethanol consumption ≥40 g for males or ≥20 g for females for 5 consecutive years; OR ② history of heavy alcohol consumption (>80 g of ethanol per day) within the past 2 weeks. Ethanol (g) = volume of alcoholic beverage consumed (mL) × alcohol by volume (%) × 0.8];
• Patients with severe concurrent cardiovascular, pulmonary, renal, endocrine, neurological, or hematological diseases, or psychiatric disorders;
• Pregnant and/or lactating women;
• Participation in any other drug clinical trial within the past 3 months;
• Any condition that, in the investigator's judgment, may affect the subject's ability to provide informed consent or comply with the trial protocol, or participation that may affect the trial results or the subject's own safety.