Clinical trial NCT05905172: Hydronidone Capsules in Long-term Treatment in Patients With Chronic Viral Hepatitis B Liver Fibrosis
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Entecavir-based, Phase IIIb Clinical Trial of Hydronidone Capsule in the Treatment of Liver Fibrosis Associated With Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Liver Fibrosis
Lead sponsor: Beijing Continent Pharmaceutical Co, Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-15
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Test group: hydronidone capsules, three times a day, 3 capsules each time，oral，daily therapeutic dose of 270 mg, half an hour before the meal

Control group: placebo capsules, three times a day, 3 capsules each time，oral，half an hour before the meal.

Basic treatment: Both test and control groups were treated with entecavir antiviral therapy, once daily, 0.5 mg per time, oral.

In case of drug resistance or other conditions requiring dose adjustment, the investigator may adjust the dose and type of basic treatment drug appropriately.
Primary purpose: TREATMENT

Brief summary: This study is a Phase IIIb extension trial following the "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".

The main objective of this study is to evaluate the effectiveness and the safety of hydronidone capsules for long-term treatment of patients with chronic viral hepatitis B liver fibrosis.

Detailed description: Nowadays, there is no satisfactory treatment and drug for liver fibrosis, so the etiology treatment of liver fibrosis and cirrhosis is the most important treatment. However, the etiology and treatment can not completely prevent the progression of liver fibrosis, and liver cirrhosis and liver cancer still occur after antiviral treatment. Although some drugs in domestic and foreign clinical trials have reported the effect of treating liver fibrosis, there is no recognized effective chemical drugs or biological agents against liver fibrosis. According to the available evidence, hydronidone capsules can effectively reduce the severity of liver fibrosis, which is expected to further reduce the risk of clinical endpoint events. Since the clinical benefit from the improvement of liver fibrosis usually takes a long time to observe, this trial takes an extended treatment approach to continuously evaluate the clinical benefit of subjects undergoing long-term treatment with hydronidone capsules in patients with liver fibrosis.

This study is a Phase IIIb extension trial following the "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". Subjects who have completed the Phase III, placebo-controlled design, double-blind, can enter the study and continue treatment according to the original treatment protocol.The aim is to evaluate the effectiveness and the safety of hydronidone capsules for long-term treatment of patients with chronic viral hepatitis B liver fibrosis.

The test group received hydronidone capsules three times a day at a daily dose of 270 mg and oral medication half an hour before the meal. The control group received placebo capsules three times a day, half an hour before the meal.Both the test and control groups received entecavir antiviral therapy as basic treatment, once daily at 0.5 mg each, by fasting oral administration. If the subject is not suitable for entecavir, the investigator will decide on the corresponding antiviral treatment according to the subject's specific condition. Discontinuation criteria for entecavir: According to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2019 edition), the American Association for the Study of Liver Disease (AASLD) and the European Association for Liver Disease (EASL) management guidelines.

Visit examination items: clinical laboratory tests (routine ALT) every 6 months (for ALT and AST, additional tests as appropriate), HBVDNA, hepatitis B, transient elastography examination, etc. In order to improve subject compliance, the investigator may increase or reduce the examination frequency or items, and at least 1 year to reducing the frequency. Additional according to the actual situation

Eligibility criteria: Inclusion Criteria:

* Participate in the Phase III trial of this project (Protocol Number: KDN-F351- 202101 ，ClinicalTrials.gov ID: NCT05115942 ), complete the main treatment course and the last visit;
* Before the trial, the subject understood the nature, significance, possible benefits, possible inconvenience and potential dangers of the trial, volunteered to participate in the clinical trial, was able to communicate well with the investigator, comply with the requirements of the whole study, and signed a written informed consent.

Exclusion Criteria:

* One of any clinical endpoints occurred during the phase III trial (Note: for non cirrhotic patients, Clinical endpoints include progression to cirrhosis,decompensated cirrhosis complications \[ascites, esophagogastric vein rupture and bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatopulmonary syndrome, hepatic encephalopathy, portal vein thrombosis and cirrhotic cardiomyopathy\], hepatocellular carcinoma, liver transplantation or liver disease related death / all-cause death; For patients with liver cirrhosis, Clinical endpoints include complications of decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, or liver disease-related death / all-cause death);
* Patients with malignant tumors other than hepatocellular carcinoma and with an expected survival period of less than 1 year;
* Any opinion of the investigator that may affect the subject to provide informed consent or follow the trial protocol, or participation in the trial may affect the trial results or their own safety.

Primary outcomes:
measure: Cumulative incidence of clinical endpoint events (defined as the occurrence of any clinical endpoint event).
timeFrame: 5years
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital Capital Medical University
state: Beijing
city: Shanghai
country: China
facility: Shanghai General Hospital,Shanghai Jiao Tong University
state: Shanghai
city: Beijing
country: China
facility: Beijing youan hospital, the capital of the capital
city: Beijing
country: China
facility: Tsinghua Changgeng Hospital, Beijing
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical University
city: Changsha
country: China
facility: The Second Xiangya Hospital, Central South University
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
city: Chongqing
country: China
facility: Three Gorges Hospital affiliated to Chongqing University
city: Guizhou
country: China
facility: Guizhou Provincial People's Hospital
city: Hangzhou
country: China
facility: Hangzhou Xixi Hospital (Hangzhou Sixth People's Hospital)
city: Henan
country: China
facility: Henan Provincial People's Hospital
city: Luzhou
country: China
facility: Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University
city: Nanchang
country: China
facility: Nanchang Ninth Hospital (Nanchang Central Hospital)
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People's Hospital)
city: Ningbo
country: China
facility: Ningbo Huamei Hospital, University of Chinese Academy of Sciences
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
city: Shenzhen
country: China
facility: Shenzhen Third People's Hospital
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical College
city: Yanbian
country: China
facility: Yanbian University Affiliated Hospital
city: Zhenjiang
country: China
facility: Zhenjiang Third People's Hospita
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
Study officials:
affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Lungen Lu, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Ditan Hospital
name: Jun Cheng, Dr
role: PRINCIPAL_INVESTIGATOR
References: