Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Viral Hepatitis B Phase 3 Trial.
- Conditions
- Liver Fibrosis
- Interventions
- Drug: The placebo capsules
- Registration Number
- NCT05115942
- Lead Sponsor
- Beijing Continent Pharmaceutical Co, Ltd.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 248
- 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.
- History of chronic hepatitis B and/or hepatitis B surface antigen (HBsAg) positive≥6 months.
- Percutaneous liver biopsy confirmed liver fibrosis (Ishak score ≥3).
- Positive HBV DNA.
- ALT < 8 x ULN (standard upper limit).
- No antiviral therapy with interferon and/or nucleoside analogues within 3 months prior to enrollment.
- 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.
- 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.
- 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.
- Massive upper gastrointestinal hemorrhage within 3 months before enrolment.
- Total bilirubin (TBiL) > 3×ULN, or 3×ULN < ALT < 8×ULN and TBiL > 2×ULN.
- AFP > 100 μg/L although there was no indication of liver cancer.
- Platelets (PLT) ≤60×109/L.
- Prothrombin activity (PTA) < 50% or INR > 1.5.
- Imaging showed obvious space-occupying lesions in the liver, suggesting tumor.
- Body mass index (BMI) > 30 kg/m2.
- Patients with decompensated liver cirrhosis and liver malignant tumor.
- Patients with chronic hepatitis C or non-viral (alcoholic, non-alcoholic, drug, etc.) chronic hepatitis.
- Serious diseases of cardiovascular, pulmonary, renal, endocrine, neurological and haematological systems, as well as mental disorders .
- Women who are pregnant and/or breastfeeding.
- Have participated in clinical trials of other drugs in the last 3 months.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description The placebo group The placebo capsules Patients were orally received placebo capsules,3 capsules each time, t.i.d. for 52 weeks. Hydronidone group Hydronidone capsules Patients were orally received hydronidone capsules,3 capsules each time, t.i.d. for 52 weeks.
- Primary Outcome Measures
Name Time Method Change in Ishak stage score of liver fibrosis by greater than or equal to 1 point after 52 weeks of treatment relative to baseline. 52 weeks 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.
- Secondary Outcome Measures
Name Time Method 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. 52 weeks 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.
Change in liver tissue inflammation grade by greater than or equal to 1 grade after 52 weeks of treatment relative to baseline. 52 weeks 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.
Change in liver stiffness measurement values via transient elastography LSM (kPa) Screening period/baseline and weeks 12, 24, 36, and 52 after treatment . Change in liver stiffness measurement values via transient elastography LSM (kPa) values relative to baseline after 52 weeks of treatment.
Negative conversion (below the lower limit of detection) and the extent of decrease in HBV DNA Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Negative conversion (below the lower limit of detection) and the extent of decrease in HBV DNA after 52 weeks of treatment.
Normalization and the degree of improvement of the indicators of liver function ALT after 52 weeks of treatment. Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after 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.
Safety endpoints:Laboratory examination（AFP test） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. AFP test: the serum AFP will be detected.
Safety endpoints:AE 52 weeks 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).Safety endpoints:Laboratory examination（Metabolic panel-AST） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Metabolic panel: The panel includes aspartate aminotransferase (AST)，which is one of the indicators to assess liver function and detect liver damage.
Safety endpoints:Laboratory examination（Metabolic panel-GGT） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Metabolic panel: The panel includes gamma-glutamyl transpeptidase (GGT),which is one of the indicators to assess liver function .
Safety endpoints:Laboratory examination（Metabolic panel-ALP） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Metabolic panel: The panel includes alkaline phosphatase (ALP),which is one of the indicators to assess liver function .
Safety endpoints:Laboratory examination（Metabolic panel-TP） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Metabolic panel: The panel includes total protein (TP), which is one of the indicators to assess liver function .
Safety endpoints:Laboratory examination（Metabolic panel-A） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Metabolic panel: The panel includes albumin (A) , which is one of the indicators to assess liver function .
Safety endpoints:Laboratory examination（Metabolic panel-TBiL） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Metabolic panel: The panel includes total bilirubin (TBiL) , which is one of the indicators to assess liver function .
Safety endpoints:Laboratory examination（Metabolic panel-DBiL） Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. Metabolic panel: The panel includes direct bilirubin (DBiL) , which is one of the indicators to assess liver function .
Trial Locations
- Locations (44)
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fujian, Fujian, China
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
🇨🇳Hefei, Anhui, China
Tsinghua Changgeng Hospital, Beijing
🇨🇳Beijing, Beijing, China
Beijing You 'an Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Chongqing Public Health Medical Treatment Center (Chongqing Infectious Disease Hospital)
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Chongqing Three Gorges Central Hospital
🇨🇳Chongqing, Chongqing, China
Lanzhou university first hospital
🇨🇳Lanzhou, Gansu, China
Xiamen Hospital of Traditional Chinese Medicine
🇨🇳Xiamen, Fujian, China
Shenzhen Third People's Hospital
🇨🇳Shenzhen, Guangdong, China
Guizhou Provincial People's Hospital
🇨🇳Guizhou, Guizhou, China
Hangzhou Xixi Hospital (Hangzhou Sixth People's Hospital)
🇨🇳Hangzhou, Hangzhou, China
Affiliated Hospital of Zunyi Medical University
🇨🇳Zunyi, Guizhou, China
Henan Provincial People's Hospital
🇨🇳Henan, Henan, China
The First Hospital of Hebei Medical University
🇨🇳Hebei, Hebei, China
The Fourth Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The Second Xiangya Hospital, Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of Xinxiang Medical College
🇨🇳Xinxiang, Henan, China
Zhengzhou Sixth People's Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Hunan University of Chinese Medicine
🇨🇳Changsha, Hunan, China
Xiangya Hospital, Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of University of South China
🇨🇳Yueyang, Hunan, China
Taizhou People's Hospital
🇨🇳Taizhou, Jiangsu, China
Nanchang Ninth Hospital (Nanchang Central Hospital)
🇨🇳Nanchang, Jiangxi, China
The First Affiliated Hospital of SuZhou University
🇨🇳Suzhou, Jiangsu, China
Wuxi Fifth People's Hospital
🇨🇳Wuxi, Jiangsu, China
Affiliated Hospital of Xuzhou Medical College
🇨🇳Xuzhou, Jiangsu, China
Zhenjiang Third People's Hospita
🇨🇳Zhenjiang, Jiangsu, China
Jiangsu Provincial People's Hospital
🇨🇳Nanjing, Jiangsu, China
First Hospital of Jilin University
🇨🇳Jilin, Jilin, China
Shanghai General Hospital,Shanghai Jiao Tong University
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Huashan Hospital affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China
Second Hospital of Jilin University
🇨🇳Jilin, Jilin, China
Yanbian University Affiliated Hospital
🇨🇳Yanbian, Jilin, China
Shanghai Jiao Tong University Affiliated Tongren Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Public Health Clinical Center
🇨🇳Shanghai, Shanghai, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China
Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University
🇨🇳Luzhou, Sichuan, China
Ningbo Huamei Hospital, University of Chinese Academy of Sciences
🇨🇳Ningbo, Zhejiang, China
Peking University First Hospital
🇨🇳Peking, Beijing, China
Beijing Ditan Hospital Capital Medical University
🇨🇳Beijing, Beijing, China