A Phase II Clinical Trial of Hydronidone Capsules(F351) in Patients With Liver Fibrosis Induced by HBV Chronic Hepatitis (HBV)

Randomed and Double-blinded Phase II Clinical Trial of Hydronidone Capsules(F351) in Patients With Liver Fibrosis Induced by HBV Chronic Hepatitis

To explore the effective dose and safety of the effect of hydronidone and entecavir on hepatic fibrosis in chronic viral hepatitis B.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Entecavir; Drug: Hydronidone

Detailed Description

Primary observation indexes:

Hepatic fibrosis Ishak score after treatment decreases by the proportion not less than 1 compared with that before treatment.

Secondary observation indexes :

1. Negative conversion ratio of HBV DNA after treatment (HBV DNA<1×103copies/mL) and falling range.
2. The falling proportion of Fibrocan Kpa value after treatment compared with that before treatment.
3. The falling proportion that decreases not less than 1 level and progression-free fibrosis after treatment compared with that before treatment.
4. The improvement of ALT of liver function.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18-65, all genders.
2. History of chronic hepatitis B, HBsAg positive≧six months.
3. ALT<eight-fold ULN (maximum).
4. Significant liver fibrosis confirmed by liver biopsy.
5. HBeAg positive patients, HBV DNA>2.0×104 IU/mL (copies/mL); HBeAg negative patients，HBV DNA>2.0×103 IU/mL (104copies/mL).
6. Having not accepted the antiviral therapy with interferon and/or nucleoside analog.
7. Having not taken anti-inflammatory drugs to protect liver within 1 month before selection.
8. Capable of understanding and signing the informed consent before the study.

Exclusion Criteria:

1. Failing to meet any one requirement of the inclusion criteria.
2. Having suffered massive hemorrhage of gastrointestinal tract within 3 months before selection
3. TBiL>three-fold ULN.
4. AFP>100 ug/L
5. PLT≦60×109/L
6. PTA<50%
7. Having obvious space-occupying lesion in liver as shown by B ultrasound examination.
8. With a portal vein ≧1.2cm wide as shown by B ultrasound examination.
9. BMI index>30.
10. The patient who suffered from liver function decompensation hepatic cirrhosis and liver neoplasms.
11. The patient with alcoholic, drug-induced, hereditary, immune and other viral and non- viral chronic hepatitis.
12. The patient with angiocarpy, lung, kidney, incretion, nerve and blood system disease and mental disease.
13. The patient with active peptic ulcer.
14. Gestational and breast feeding women.
15. The subject is the legal disabled person according to the Law of the People's Republic of China on the Protection of Disabled Persons of the April 2008 edition.
16. The subject who participated in other drug tests within recent 3 months.
17. The patient who is suspected with poor compliance or disagrees to participate in the test.
18. The patient who is considered by other investigators not to be suitable for participating in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydronidone(180mg) & Entecavir & Placebo; hydronidone capsule 30mg/capsule hydronidone capsule, three times a day, 2 capsules each time; with co-administration of placebo capsule, three times a day, 2 capsules each time, namely the daily dose of the investigational product is 180mg. The test groups and the control group take the entecavir capsule which is orally taken for antiviral therapy, one time a day, 0.5mg each time, oral administration on an empty stomach.	Drug: Placebo; Drug: Entecavir; Drug: Hydronidone; The investigational products in the test groups and control group shall be orally taken 30 minutes before meals for 52 continuous weeks. There are respectively 60 cases in the test group I, II, III and the control group, totally 240 cases.; Other Names: F351
Experimental: Hydronidone(270mg) & Entecavir & Placebo; hydronidone capsule 30mg/capsule hydronidone capsule, three times a day, 3 capsules each time; with co-administration of placebo capsule, three times a day, 1 capsules each time, namely the daily dose of the investigational product is 270mg. The test groups and the control group take the entecavir capsule which is orally taken for antiviral therapy, one time a day, 0.5mg each time, oral administration on an empty stomach.	Drug: Placebo; Drug: Entecavir; Drug: Hydronidone; The investigational products in the test groups and control group shall be orally taken 30 minutes before meals for 52 continuous weeks. There are respectively 60 cases in the test group I, II, III and the control group, totally 240 cases.; Other Names: F351
Experimental: Hydronidone(360mg) & Entecavir; hydronidone capsule 30mg/capsule hydronidone capsule, three times a day, 4 capsules each time; namely the daily dose of the investigational product is 360mg. The test groups and the control group take the entecavir capsule which is orally taken for antiviral therapy, one time a day, 0.5mg each time, oral administration on an empty stomach.	Drug: Entecavir; Drug: Hydronidone; The investigational products in the test groups and control group shall be orally taken 30 minutes before meals for 52 continuous weeks. There are respectively 60 cases in the test group I, II, III and the control group, totally 240 cases.; Other Names: F351
Experimental: Entecavir & Placebo(360mg); placebo capsule 30mg/capsule placebo capsule, three times a day, 4 capsules each time. The test groups and the control group take the entecavir capsule which is orally taken for antiviral therapy, one time a day, 0.5mg each time, oral administration on an empty stomach.	Drug: Placebo; Drug: Entecavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in hepatic fibrosis in chronic viral hepatitis B	one year

Collaborators and Investigators

• Sponsor: Shanghai Genomics, Inc.
• Investigators: Principal Investigator: LunGen Lu, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Principal Investigator: Jun Cheng, Beijing Ditan Hospital

Publications and helpful links

General Publications

• Cai X, Liu X, Xie W, Ma A, Tan Y, Shang J, Zhang J, Chen C, Yu Y, Qu Y, Zhang L, Luo Y, Yin P, Cheng J, Lu L. Hydronidone for the Treatment of Liver Fibrosis Related to Chronic Hepatitis B: A Phase 2 Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Jul 13:S1542-3565(22)00650-4. doi: 10.1016/j.cgh.2022.05.056. Online ahead of print.

Study record dates

Study Major Dates

• Study Start: June 25, 2015
• Primary Completion (Actual): November 20, 2020
• Study Completion (Actual): November 20, 2020

Study Registration Dates

• First Submitted: June 26, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (Estimate): July 16, 2015

Study Record Updates

• Last Update Posted (Actual): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 21, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Fibrosis; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Liver Cirrhosis; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: GNI-F351-201402