Clinical trial NCT05115942: Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Viral Hepatitis B Phase 3 Trial.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Fibrosis
Lead sponsor: Beijing Continent Pharmaceutical Co, Ltd.
Sponsor class: INDUSTRY
First posted: 2021-11-10
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Ishak stage score of liver fibrosis by greater than or equal to 1 point after 52 weeks of treatment relative to baseline.
timeFrame: 52 weeks
Secondary outcomes:
measure: 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.
timeFrame: 52 weeks
measure: Change in liver tissue inflammation grade by greater than or equal to 1 grade after 52 weeks of treatment relative to baseline.
timeFrame: 52 weeks
measure: Change in liver stiffness measurement values via transient elastography LSM (kPa)
timeFrame: Screening period/baseline and weeks 12, 24, 36, and 52 after treatment .
measure: Negative conversion (below the lower limit of detection) and the extent of decrease in HBV DNA
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Normalization and the degree of improvement of the indicators of liver function ALT after 52 weeks of treatment.
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:Laboratory examination（AFP test）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:AE
timeFrame: 52 weeks
measure: Safety endpoints:Laboratory examination（Metabolic panel-AST）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:Laboratory examination（Metabolic panel-GGT）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:Laboratory examination（Metabolic panel-ALP）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:Laboratory examination（Metabolic panel-TP）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:Laboratory examination（Metabolic panel-A）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:Laboratory examination（Metabolic panel-TBiL）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
measure: Safety endpoints:Laboratory examination（Metabolic panel-DBiL）
timeFrame: Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment.
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
state: Anhui
city: Beijing
country: China
facility: Beijing Ditan Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing You 'an Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Tsinghua Changgeng Hospital, Beijing
state: Beijing
city: Peking
country: China
facility: Peking University First Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Public Health Medical Treatment Center (Chongqing Infectious Disease Hospital)
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Three Gorges Central Hospital
state: Chongqing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Fujian
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: Xiamen Hospital of Traditional Chinese Medicine
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou university first hospital
state: Gansu
city: Shenzhen
country: China
facility: Shenzhen Third People's Hospital
state: Guangdong
city: Guizhou
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Hangzhou
country: China
facility: Hangzhou Xixi Hospital (Hangzhou Sixth People's Hospital)
state: Hangzhou
city: Hebei
country: China
facility: The First Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Henan
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical College
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Sixth People's Hospital
state: Henan
city: Changsha
country: China
facility: The First Affiliated Hospital of Hunan University of Chinese Medicine
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital, Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Yueyang
country: China
facility: The First Affiliated Hospital of University of South China
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of SuZhou University
state: Jiangsu
city: Taizhou
country: China
facility: Taizhou People's Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi Fifth People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical College
state: Jiangsu
city: Zhenjiang
country: China
facility: Zhenjiang Third People's Hospita
state: Jiangsu
city: Nanchang
country: China
facility: Nanchang Ninth Hospital (Nanchang Central Hospital)
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Jilin
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Jilin
country: China
facility: Second Hospital of Jilin University
state: Jilin
city: Yanbian
country: China
facility: Yanbian University Affiliated Hospital
state: Jilin
city: Shanghai
country: China
facility: Shanghai General Hospital,Shanghai Jiao Tong University
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Jiao Tong University Affiliated Tongren Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
city: Shanghai
country: China
facility: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Luzhou
country: China
facility: Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University
state: Sichuan
city: Ningbo
country: China
facility: Ningbo Huamei Hospital, University of Chinese Academy of Sciences
state: Zhejiang
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: