A Phase II of Randomized, Double-blind, Placebo-controlled, Multi-center Study of Hepalatide for Injection Combined With Pegylated Interferon and TAF as Finite Treatment in Chronic Hepatitis B Patients
A Phase II of Randomized, Double-blind, Placebo-controlled, Multi-center Study of Hepalatide for Injection Combined With Pegylated Interferon and TAF as Finite Treatment in Chronic Hepatitis B Patients
The study is designed to assess efficacy of a finitie treatment in Chronic Hepatitis B patients who had stable treatment of NAs for ≧ 2 years， which is compared hepalatide in combination with Pegylated Interferon + TAF with Pegylated Interferon +TAF. Subjects will be randomly assigned to the hepalatide or placebo groups , 15 subjects in each group . Subjects will receive hepalatide+Pegylated Interferon +TAF treatment for 48 weeks or placebo +PegylatedInterferon +TAF treatment for 48 weeks , Then, stopping hepalatide and Pegylate Interferon treatments and followed with further 8 weeks follow-up.
Hepalatide is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection. The aim of this study is to assess efficacy of a finitie treantment , that combination regimen of hepalatide+half dose Pegylated interferon + TAF , as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4weeks), Treatment Period (48 weeks) and Follow-up (FU) Period (8 weeks). Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 60 weeks (including screening period).
Inclusion Criteria:
1. HBsAg or/and HBV DNA Positive for at least 6 months
2. HBeAg negative
3. Received NAs stabilization therapy for at least 2 years
4. ALT≤ 2×ULN
5. HBV DNA< LLQD(lower limit of quantitative detection) in Screening
6. Serum total bilirubin<2×ULN
7. no childbirth plan within 2 years and agree to take effective contraceptive measures throughout the treatment period and within 3 months after the last dose, and that the woman is not pregnant or breastfeeding.
8. have not participant in another clinical trial within 3 months before screening
9. Subjects have good compliance with the protocol
10. Subjects understood and agreed to sign the informed consent form.
Exclusion Criteria:
1. Contraindications of Peginterferon such as depressive disorder, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction, etc
2. Subjects with cirrhosis, e.g., definite cirrhosis on imaging such as abdominal ultrasound and CT; liver biopsy with Metavir fibrosis score = 4; clinical diagnosis of cirrhosis by the investigator.
3. Decompensated liver disease
4. Child-Pugh score of B-C or over 6 points.
5. Subjects with any of the following circumstances
History of decompensated liver disease
History of serious heart disease (including unstable or uncontrolled heart disease within 6 months)
Uncontrolled seizures, severe psychiatric disorders, or a history of psychiatric disorders
with history of organ transplantation
with poorly controlled diabetes and hypertension
with autoimmune diseases, immune-related extrahepatic manifestations, thyroid disease, malignant tumors, or in immunosuppressive therapy
underlying diseases such as malignant tumor, severe infection, heart failure and chronic obstructive pulmonary disease and other serious diseases.
with history of alcohol or drug abuse
6. Creatinine clearance <60 mL/min.
7. HAV, HCV, HDV, HEV or HIV co-infection
8. Subjects who must be treated with Nucleosides (acids) other than TAF during treatment period
9. Subjects who used interferon in the 6 months prior to the screening period
10. Positive for anti-HBV Pre-S1 antibody.
11. Hemocytopenia: White blood cells < 3 × 10^9 / L, neutrophil < 1.5 × 10^9 / L, platelet < 60 × 10^9 / L,
12. Female subjects pregnancy test positive
13. known to be allergic to the investigational drug or the underlying treatment drug
14. Other laboratories or auxiliary examinations are obviously abnormal