The goal of this a clinical trial is to learn about the efficacy,safety and Pharmacokinetics of Hepenofovir Fumarate Tablets(HTS) in patients with CHB. The main questions it aims to answer are: 1. Evaluate the efficacy and safety of multiple doses of continuous administration of HTS in patients with chronic hepatitis B, and compare it with Tenofovir alafenamide Fumarate tablets(TAF). 2. To evaluate the pharmacokinetic characteristics of HTS in patients with chronic hepatitis B after multiple oral administration. 3. To evaluate the pharmacodynamic changes of HTS in patients with chronic hepatitis B after multiple consecutive administrations, and compare it with TAF. Positive control drug:Tenofovir alafenamide Fumarate tablets(25mg/d) Test drug:Hepenofovir Fumarate Tablets(10mg/d、20mg/d、40mg/qod) Test process:This study was divided into 4 groups, with the specific list shown below. The initial plan was to include 12 subjects in each group, stratified by HBeAg status, with 4 subjects negative for HBeAg and 8 subjects positive for HBeAg. A total of 48 subjects were included in this trial, and they were randomly assigned to multiple doses at a ratio of 1:1:1:1. The dosing period was 24 weeks. However, after enrolling 37 subjects (29 positive for HBeAg and 8 negative for HBeAg), the protocol was adjusted (V4.0): the remaining 11 subjects would be included, all of whom were over 30 years old with ALT \< ULN and met all the inclusion criteria but none of the exclusion criteria. The random assignment was: 7 subjects positive for HBeAg were randomly assigned to HTS 10mg/day, 20mg/day, 40mg/qod and TAF 25mg/day groups at a ratio of 2:2:2:1; and 4 subjects negative for HBeAg were randomly assigned to HTS 10mg/day, 20mg/day, 40mg/qod and TAF 25mg/day groups at a ratio of 1:1:1:1.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Each subject received multiple doses of the test drug/control drug and completed safety, efficacy, and PK evaluations
The First Hospital of Jilin University
Jilin, Changchun, China
RECRUITINGQuantification of HBV DNA
HBV DNA
Time frame: Screening period,week2(Day15±3),week4(Day29±3),week8(Day57±3),week12 (Day85±5),week16(Day113±5),week20(Day141±5),week24(Day169±5),week28(Day197±5), week32(Day225±5),week36(Day253±5),week40(Day281±5),week44(Day309±5),week48(Day335 QOD or Day336QD ±5)
Quantification of HBV markers
HBsAg ,HBeAg
Time frame: Day1 before administration,week12(Day85±5),week24(Day169±5), week36(Day253±5),week48(Day335 QOD or Day336QD ±5)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Symptoms and physical examination, clinical laboratory tests (blood routine, blood biochemistry, coagulation profile, urine routine, thyroid function test), thyroid ultrasound, abdominal ultrasound, vital signs (blood pressure, pulse, respiration and body temperature), 12-lead electrocardiogram, bone density, monitoring and recording of adverse events and concomitant medication.
Time frame: during the intervention、within 4 weeks of completion of treatment
Area Under the Plasma Concentration Versus Time Curve (AUC) of HTS and TFV
The experimental group measured the concentrations of hepranofovir and tenofovir (TFV), while the control group measured the concentrations of tenofovir (TFV)
Time frame: 0min,15min,30min,1hour,1.25hour,1.5hour,2hour,2.5hour,3hour,4hour,5hour,6hour,8hour,12hour,24hour,48hour
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