A Single-center, Randomized, Open-label, Active-controlled Phase Ic/IIb Study to Evaluate the Efficacy，Safety and Pharmacokinetics of Hepenofovir Fumarate Tablets in Patients With CHB
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.
• Subjects voluntarily sign the informed consent form.
• Subjects (including partners) are willing to have no plans for pregnancy from the time of screening to 3 months after the last administration of the study drug and ensure appropriate contraception measures are taken.
• Male or female subjects (including boundary values) between 18-65 years of age, regardless of gender.
• Body mass index (BMI) between 18.0-32.0 kg/m2 (including critical values), where BMI = body weight (kg) / height2 (m2).
• Evidence (including but not limited to outpatient/inpatient medical records/laboratory reports, etc.) to prove a history of positive hepatitis B surface antigen (HBsAg) or positive HBV DNA for at least 6 months at the time of screening, or negative HBcAb IgM and positive HBsAg at the time of screening, or histological examination of liver tissue showing chronic hepatitis B infection.
• HBeAg-positive patients with HBV DNA ≥ 2.0×104 IU/mL and HBeAg-negative patients with HBV DNA ≥ 2.0×103 IU/mL at the time of screening.
• Subjects with ALT between 1.2×ULN and 10×ULN within 7 days of screening, or subjects over 30 years of age with ALT less than 1.2×ULN; total bilirubin (TBIL) ≤ 2×ULN;
• Creatinine clearance rate ≥ 70 mL/min \[calculation formula: Ccr: (140-age)×weight (kg) / (0.818×Scr) (μmol/L), female×0.85\];
• Subjects who have not used anti-HBV nucleotide/nucleoside therapy, interferon therapy, or immunomodulators within the previous 6 months prior to screening;
⁃ Subjects who fully understand the trial process, possible adverse reactions, and can complete the trial according to the protocol plan.