A Study of Hydronidone Capsules in Patients With Chronic Hepatitis B Virus-Related Liver Fibrosis

A Phase II, Single-Arm, Open-Label, Multicenter Clinical Trial Evaluating the Safety of Hydronidone Capsules in Patients With Chronic Hepatitis B Virus-Related Liver Fibrosis

This trial employs a single-arm, open-label, multicenter clinical trial design. All study participants who meet the inclusion/exclusion criteria will receive Hydronidone treatment for 4 weeks. The study includes a screening period (up to 21 days) to assess the eligibility of participants. Eligible participants will enter the treatment period and receive Hydronidone capsules at a dosage of 270 mg TID (30 mg/capsule, 3 capsules each time, three times daily, taken orally half an hour before meals) for 28 consecutive days. Participants will return for a follow-up visit on Day 28 (±3 days) after the first dose for safety assessments. All adverse events (AEs) and concomitant medications occurring during the study period must be recorded. After the treatment period, participants will enter a follow-up period to monitor any delayed adverse events. Participants who complete the final follow-up visit are considered to have completed the study. Throughout the study, participants must maintain the stability of all their pre-existing treatment regimens, including antiviral therapy and medications for other comorbid conditions.

Inclusion Criteria:

• Age 18 to 70 years (inclusive of 18 and 70 years old, based on the date of signing the informed consent form), regardless of gender.

• History of chronic hepatitis B and/or Hepatitis B surface antigen (HBsAg) positive for ≥6 months.

• Diagnosed with chronic hepatitis B-related fibrosis by the investigator, meeting any of the following criteria:

  1. Liver biopsy histopathological examination (results from within 12 months prior to screening are acceptable) with an Ishak score ≥3 or Metavir score ≥F2;
  2. Liver stiffness measurement (Fibroscan, Fibrotouch, or ILivTouch; results from within 1 month prior to screening are acceptable) with a liver stiffness value ≥9.0 kPa;
  3. Imaging examination (results from within 12 months prior to screening are acceptable), such as abdominal ultrasound, CT, or MRI, indicating morphological features of cirrhosis (e.g., irregular liver surface, liver lobe disproportion, etc.).

• Currently receiving stable antiviral therapy with one or two drugs such as ETV (Entecavir), TAF (Tenofovir Alafenamide), TDF (Tenofovir Disoproxil Fumarate), or TMF (Tenofovir Mefenamide) for ≥6 months.

• The study participant agrees, from the time of signing the informed consent form until 6 months after the last dose of the study drug, to voluntarily adopt effective contraception for themselves and their partner, with no plans for pregnancy, sperm donation, or egg donation during this period.

• Prior to the trial, the participant has fully understood the nature, significance, potential benefits, possible inconveniences, and risks of the study, voluntarily agrees to participate in this clinical trial, can communicate well with the investigator, adheres to all study requirements, and has signed a written informed consent form.

Exclusion Criteria:

• Individuals with a history of specific allergies (e.g., asthma, urticaria, eczema), an allergic constitution (e.g., allergy to drugs or food), or known allergy to Hydroxynidone, pirfenidone, any of their components, or excipients.

• Individuals currently suffering from the following serious concurrent diseases:

  1. Cardiovascular System: Uncontrolled heart failure (NYHA Class III-IV), unstable angina, myocardial infarction within the past 6 months, uncontrolled hypertension, etc.
  2. Renal Diseases: Severe renal insufficiency (eGFR <30 mL/min/1.73 m²), end-stage renal disease, acute kidney injury, etc.
  3. Endocrine and Metabolic Diseases: Poorly controlled diabetes (HbA1c >8.5%), thyroid crisis, etc.
  4. Other Chronic Liver Diseases: Alcoholic liver disease, drug-induced liver injury, autoimmune liver disease, or severe hepatic steatosis (CAP ≥295 dB/m).
  5. Individuals currently receiving anti-tuberculosis treatment or diagnosed with active tuberculosis.

• Individuals with a history of decompensated liver cirrhosis (e.g., ascites, hepatic encephalopathy, history of esophageal and gastric variceal bleeding) within 12 months prior to screening, patients with clinically diagnosed liver malignancy, or those with other confirmed malignancies.

• Individuals with a history of major upper gastrointestinal bleeding within 6 months prior to screening; those scheduled or requiring immediate upper gastrointestinal endoscopy (gastroscopy) during the trial due to portal hypertension; or cACLD patients with liver stiffness measurement ≥20 kPa and/or platelet count ≤150×10⁹/L.

• Individuals with abnormal laboratory test results or clinically significant abnormalities as judged by the investigator:

Total bilirubin (TBIL) >3 × ULN, or 3 × ULN < ALT <8 × ULN and TBIL >2 × ULN.

ALT ≥8 × ULN.

Platelet count (PLT) ≤50 × 10⁹/L.

Prothrombin activity (PTA) <40% or International Normalized Ratio (INR) >1.5.

• Individuals with a body mass index (BMI) >32 kg/m².

• Individuals with alpha-fetoprotein (AFP) >100 μg/L in the absence of indicators suggesting hepatocellular carcinoma.

• Concurrent users of the following medications:

  1. Currently using interferon.
  2. Use of known CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) or inducers (e.g., rifampicin, omeprazole) prior to screening, with a washout period less than 7 half-lives of the respective drug.
  3. Use of complex traditional Chinese herbal formulations, herbal medicines, or health supplements with unclear interaction profiles.

• Individuals with a history of or currently suffering from severe depression, post-traumatic stress disorder (PTSD), other serious mental disorders (e.g., schizophrenia, bipolar disorder, etc.), or cognitive impairment, who are unable to cooperate with medication administration and follow-up.

• Individuals with dysphagia, swallowing disorders, or diseases affecting digestion and absorption, such as inflammatory bowel disease, short bowel syndrome, etc.

• Individuals testing positive for human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, or hepatitis C virus (HCV) antibody.

• Individuals with a history of drug abuse, alcohol abuse, or drug dependence (including methadone maintenance therapy) within 12 months prior to screening.

• Pregnant or lactating women.

• Individuals who do not agree, from the time of signing the informed consent until 6 months after the last dose of the study drug, to voluntarily adopt effective contraception for themselves and their partner, and have no plans for pregnancy, sperm donation, or egg donation during this period.

• Individuals who have participated in other clinical trials and used investigational drugs or medical devices within 3 months prior to screening.

• Individuals unable to complete the trial for other reasons, or those deemed unsuitable for participation by the investigator due to other factors.