Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Viral Hepatitis B Phase 3 Trial.

A Randomized, Double-blind, Placebo-controlled, Multicenter, Entecavir-based, Phase III Clinical Trial of Hydronidone Capsule in the Treatment of Liver Fibrosis Associated with Chronic Hepatitis B

This study was a randomized, double-blind, placebo-controlled, entecavir basic treatment, multicentre clinical study.

The main objective of this study was to confirm the efficacy and safety of hydronidone in the treatment of chronic hepatitis B liver fibrosis.

Study Overview

• Status: Completed
• Conditions: Liver Fibrosis
• Intervention / Treatment: Drug: Hydronidone capsules; Drug: The placebo capsules

Detailed Description

248 patients with chronic viral hepatitis B liver fibrosis were enrolled in this 52-week study, and randomized into hydronidone or placebo group. Each group has 124 patients. Both groups were treated with entecavir antiviral basic therapy.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China
      • The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
  • Beijing
    • Beijing, Beijing, China, 100020
      • Beijing Ditan Hospital Capital Medical University
    • Beijing, Beijing, China
      • Beijing You 'an Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Tsinghua Changgeng Hospital, Beijing
    • Peking, Beijing, China
      • Peking University First Hospital
  • Chongqing
    • Chongqing, Chongqing, China
      • The First Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China
      • Chongqing Three Gorges Central Hospital
    • Chongqing, Chongqing, China
      • Chongqing Public Health Medical Treatment Center (Chongqing Infectious Disease Hospital)
  • Fujian
    • Fujian, Fujian, China
      • The First Affiliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China
      • Xiamen Hospital of Traditional Chinese Medicine
  • Gansu
    • Lanzhou, Gansu, China
      • Lanzhou University First Hospital
  • Guangdong
    • Shenzhen, Guangdong, China
      • Shenzhen Third People's Hospital
  • Guizhou
    • Guizhou, Guizhou, China
      • Guizhou Provincial People's Hospital
    • Zunyi, Guizhou, China
      • Affiliated Hospital of Zunyi Medical University
  • Hangzhou
    • Hangzhou, Hangzhou, China
      • Hangzhou Xixi Hospital (Hangzhou Sixth People's Hospital)
  • Hebei
    • Hebei, Hebei, China
      • The First Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Henan, Henan, China
      • Henan Provincial People's Hospital
    • Xinxiang, Henan, China
      • The First Affiliated Hospital of Xinxiang Medical College
    • Zhengzhou, Henan, China
      • Zhengzhou Sixth People's Hospital
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Hospital, Central South University
    • Changsha, Hunan, China
      • The Second Xiangya Hospital, Central South University
    • Changsha, Hunan, China
      • The First Affiliated Hospital of Hunan University of Chinese Medicine
    • Yueyang, Hunan, China
      • The First Affiliated Hospital of University of South China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Provincial People's Hospital
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Suzhou University
    • Taizhou, Jiangsu, China
      • Taizhou People's Hospital
    • Wuxi, Jiangsu, China
      • Wuxi Fifth People's Hospital
    • Xuzhou, Jiangsu, China
      • Affiliated Hospital of Xuzhou Medical College
    • Zhenjiang, Jiangsu, China
      • Zhenjiang Third People's Hospita
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital Of Nanchang University
    • Nanchang, Jiangxi, China
      • Nanchang Ninth Hospital (Nanchang Central Hospital)
  • Jilin
    • Jilin, Jilin, China
      • First Hospital of Jilin University
    • Jilin, Jilin, China
      • Second Hospital of Jilin University
    • Yanbian, Jilin, China
      • Yanbian University Affiliated Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Public Health Clinical Center
    • Shanghai, Shanghai, China
      • Huashan Hospital Affiliated to Fudan University
    • Shanghai, Shanghai, China
      • Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
    • Shanghai, Shanghai, China, 201620
      • Shanghai General Hospital,Shanghai Jiao Tong University
    • Shanghai, Shanghai, China
      • Shanghai Jiao Tong University Affiliated Tongren Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
    • Luzhou, Sichuan, China
      • Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University
  • Zhejiang
    • Ningbo, Zhejiang, China
      • Ningbo Huamei Hospital, University of Chinese Academy of Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age from 18 to 65 years old (including 18 and 65 years old, based on the time of signing the written informed consent); gender is not limited.
2. History of chronic hepatitis B and/or hepatitis B surface antigen (HBsAg) positive≥6 months.
3. Percutaneous liver biopsy confirmed liver fibrosis (Ishak score ≥3).
4. Positive HBV DNA.
5. ALT < 8 x ULN (standard upper limit).
6. No antiviral therapy with interferon and/or nucleoside analogues within 3 months prior to enrollment.
7. 3 months before inclusion, he/she had not received any of the following proprietary Chinese medicines that may have anti-fibrosis effects: Fuzheng Huayu Capsule (tablet), Anluo Huayu Pill, compound Bijiaruangan tablet, etc.
8. The subject (or his/her sexual partner) had no pregnancy plan during the trial period and within 6 months after the trial, voluntarily used effective physical contraception, and had no sperm or egg donation plan.
9. Before the trial, they have understood the nature, significance, potential benefits, inconvenience and potential dangers of the trial in detail, and have voluntarily participated in the clinical trial, have good communication with the researchers, comply with the requirements of the whole study, and have signed a written informed consent form.

Exclusion Criteria:

1. Massive upper gastrointestinal hemorrhage within 3 months before enrolment.
2. Total bilirubin (TBiL) > 3×ULN, or 3×ULN < ALT < 8×ULN and TBiL > 2×ULN.
3. AFP > 100 μg/L although there was no indication of liver cancer.
4. Platelets (PLT) ≤60×109/L.
5. Prothrombin activity (PTA) < 50% or INR > 1.5.
6. Imaging showed obvious space-occupying lesions in the liver, suggesting tumor.
7. Body mass index (BMI) > 30 kg/m2.
8. Patients with decompensated liver cirrhosis and liver malignant tumor.
9. Patients with chronic hepatitis C or non-viral (alcoholic, non-alcoholic, drug, etc.) chronic hepatitis.
10. Serious diseases of cardiovascular, pulmonary, renal, endocrine, neurological and haematological systems, as well as mental disorders .
11. Women who are pregnant and/or breastfeeding.
12. Have participated in clinical trials of other drugs in the last 3 months.
13. The Investigator considers that there are any conditions that may affect the subjects' informed consent or adherence to the study protocol, or participation in the study may affect the study results or their own safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydronidone group; Patients were orally received hydronidone capsules,3 capsules each time, t.i.d. for 52 weeks.	Drug: Hydronidone capsules; After randomization, the experimental group were orally received hydronidone capsules at a daily dose of 270 mg, 3 capsules each time, t.i.d,30 min before meals for 52 weeks.; Other Names: F351
Placebo Comparator: The placebo group; Patients were orally received placebo capsules,3 capsules each time, t.i.d. for 52 weeks.	Drug: The placebo capsules; After randomization, The control group were orally received placebo capsules at a daily dose of 270 mg, 3 capsules each time, t.i.d, 30 min before meals for 52 weeks.; Other Names: N

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ishak stage score of liver fibrosis by greater than or equal to 1 point after 52 weeks of treatment relative to baseline.	Clinically, the liver pathology scoring system, Ishak system, is widely used make a detailed and accurate assessment of the degree of parenchymal fibrosis or cirrhosis of the nontumorous liver. Ishak system uses a scale of 7 stages (scores 0-6) for the degree of fibrosis; the higher the score, the higher degree the severity of the disease.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver inflammation grade by greater than or equal to 1 grade after 52 weeks of treatment relative to baseline but with no progression of fibrosis.	Scheuer score system is a liver pathology scoring system used for the diagnosis of liver inflammation and fibrosis pathology clinically; In the present trial, Scheuer system for scoring necroinflammatory activitt in chronic hepatitis will be used(G0-G4),the higher the score, the higher degree the severity of the disease.	52 weeks
Change in liver tissue inflammation grade by greater than or equal to 1 grade after 52 weeks of treatment relative to baseline.	Scheuer score system is a liver pathology scoring system used for the diagnosis of liver inflammation and fibrosis pathology clinically; In the present trial, Scheuer system for scoring necroinflammatory activitt in chronic hepatitis will be used(G0-G4),the higher the score, the higher degree the severity of the disease.	52 weeks
Change in liver stiffness measurement values via transient elastography LSM (kPa)	Change in liver stiffness measurement values via transient elastography LSM (kPa) values relative to baseline after 52 weeks of treatment.	Screening period/baseline and weeks 12, 24, 36, and 52 after treatment .
Negative conversion (below the lower limit of detection) and the extent of decrease in HBV DNA	Negative conversion (below the lower limit of detection) and the extent of decrease in HBV DNA after 52 weeks of treatment.	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Normalization and the degree of improvement of the indicators of liver function ALT after 52 weeks of treatment.	ALT is one of the indicators to assess liver function and detect liver damage. When hepatic cells are affected by injury or disease, ALT is released into the blood, resulting in elevated ALT levels in the blood.	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:Laboratory examination（AFP test）	AFP test: the serum AFP will be detected.	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:AE	Adverse events (AEs) refer to any adverse medical events that occur after the patient takes the study drug and can manifest as signs and symptoms, disease, or abnormal laboratory tests, but are not necessarily consequently related to the study drug. Information on AEs and Concomitant medications occurring in patients will be collected at the time points specified in the study schedule. AEs will be evaluated with reference to the Common Adverse Events Evaluation Criteria (NCI-CTCAE version 5.0).	52 weeks
Safety endpoints:Laboratory examination（Metabolic panel-AST）	Metabolic panel: The panel includes aspartate aminotransferase (AST)，which is one of the indicators to assess liver function and detect liver damage.	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:Laboratory examination（Metabolic panel-GGT）	Metabolic panel: The panel includes gamma-glutamyl transpeptidase (GGT),which is one of the indicators to assess liver function .	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:Laboratory examination（Metabolic panel-ALP）	Metabolic panel: The panel includes alkaline phosphatase (ALP),which is one of the indicators to assess liver function .	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:Laboratory examination（Metabolic panel-TP）	Metabolic panel: The panel includes total protein (TP), which is one of the indicators to assess liver function .	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:Laboratory examination（Metabolic panel-A）	Metabolic panel: The panel includes albumin (A) , which is one of the indicators to assess liver function .	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:Laboratory examination（Metabolic panel-TBiL）	Metabolic panel: The panel includes total bilirubin (TBiL) , which is one of the indicators to assess liver function .	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Safety endpoints:Laboratory examination（Metabolic panel-DBiL）	Metabolic panel: The panel includes direct bilirubin (DBiL) , which is one of the indicators to assess liver function .	Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.

Collaborators and Investigators

• Sponsor: Beijing Continent Pharmaceutical Co, Ltd.
• Investigators: Principal Investigator: Lungen Lu, Dr., Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Principal Investigator: Jun Cheng, Dr., Beijing Ditan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Actual): October 22, 2024
• Study Completion (Actual): October 22, 2024

Study Registration Dates

• First Submitted: October 9, 2021
• First Submitted That Met QC Criteria: October 29, 2021
• First Posted (Actual): November 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Fibrosis; Hepatitis B; Liver Cirrhosis
• Other Study ID Numbers: KDN-F351-202101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No