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

Sponsor

Shanghai Genomics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02499562

Collaborator

(none)

168

Enrollment

Locations

Arms

64.9

Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: Hydronidone Drug: Placebo Drug: Entecavir	Phase 2

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 :

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

Study Design

Study Type:

Interventional

Actual Enrollment :

168 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 25, 2015

Actual Primary Completion Date :

Nov 20, 2020

Actual Study Completion Date :

Nov 20, 2020

Arms and Interventions

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: 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 Drug: Placebo Drug: Entecavir
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: 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 Drug: Placebo Drug: Entecavir
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: 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 Drug: Entecavir
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

Outcome Measures

Primary Outcome Measures

Changes in hepatic fibrosis in chronic viral hepatitis B [one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Failing to meet any one requirement of the inclusion criteria.
Having suffered massive hemorrhage of gastrointestinal tract within 3 months before selection
TBiL>three-fold ULN.
AFP>100 ug/L
PLT≦60×109/L
PTA<50%
Having obvious space-occupying lesion in liver as shown by B ultrasound examination.
With a portal vein ≧1.2cm wide as shown by B ultrasound examination.
BMI index>30.
The patient who suffered from liver function decompensation hepatic cirrhosis and liver neoplasms.
The patient with alcoholic, drug-induced, hereditary, immune and other viral and non- viral chronic hepatitis.
The patient with angiocarpy, lung, kidney, incretion, nerve and blood system disease and mental disease.
The patient with active peptic ulcer.
Gestational and breast feeding women.
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.
The subject who participated in other drug tests within recent 3 months.
The patient who is suspected with poor compliance or disagrees to participate in the test.
The patient who is considered by other investigators not to be suitable for participating in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shanghai General Hospital	Shanghai	Shanghai	China
2		Beijing		China

Sponsors and Collaborators

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