A Study of Hepalatide Combined With TAF and PEG-IFN as Finite Treatment of Chronic Hepatitis B Patients

Study Overview
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Brief Summary
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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 all treatments and followed with further 24 weeks follow-up.

Detailed Description
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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 (24 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 76 weeks (including screening period).

Official Title
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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

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Hepalatide
* Drug: Placebo of Hepalatide
* Drug: Tenofovir Alafenamide Tablets
* Drug: Pegylated Interferon alfa 2a


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hepalatide + TAF + PEG-IFN<br>Patients will receive 4.2mg Hepalatide +25mg Tenofovir alafenamide+ 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks. | Drug: Hepalatide<br>* 4.2mg, s.c., qd for 48 weeks<br>* Other names: L47;Drug: Tenofovir Alafenamide Tablets<br>* 25mg, p.o., qd for 48 weeks<br>* Other names: Vemlidy;Drug: Pegylated Interferon alfa 2a<br>* 90ug, s.c., qw for 48 weeks<br>* Other names: Pegasys;|
| Placebo Comparator: Placebo+ TAF + PEG-IFN<br>Patients will receive Placebo +25mg Tenofovir alafenamide + 90ug Pegylated Interferon for 48 weeks with a further follow-up period of 24 weeks. | Drug: Placebo of Hepalatide<br>* s.c., qd for 48 weeks<br>* Other names: Placebo;Drug: Tenofovir Alafenamide Tablets<br>* 25mg, p.o., qd for 48 weeks<br>* Other names: Vemlidy;Drug: Pegylated Interferon alfa 2a<br>* 90ug, s.c., qw for 48 weeks<br>* Other names: Pegasys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with sustained viral response at 48 weeks off treatment | HBV DNA<20 IU/ml | 96 Weeks | 
| Proportion of subjects with negative conversion of HBsAg | Proportion of subjects with negative conversion of HBsAg treatment at 48 weeks off treatment | 96 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with retreatment with NAs | Number of subjects with retreatment with NAs at 48 weeks off treatment | 96 Weeks | 
| Number of subjects with virological relapse(VR) at 48 weeks off treatment | VR: reappearance of HBV DNA > 2000 IU/ml from undetectable status | 96 Weeks | 
| Number of subjects with clinical relapse(CR) at 48 weeks off treatment | CR: the presence of VR with the elevation of alanine transaminase (ALT) more than two times upper limit of normal (ULN) | 96 Weeks | 
| HBsAg is down from baseline at 48 weeks off treatment | HBsAg is down from baseline log10 | 96 Weeks | 
| Number of subjects with Serological conversion of HBsAg | Number of subjects with Serological conversion of HBsAg at 48 weeks off treatment | 96 Weeks | 
| Change in liver stiffness at 24 weeks off treatment | The findings of Liver stiffness measurement(LSM) of Fibroscan/FibroTouch at week 48 off treatment compared to baseline | 96 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepalatide, Hepatitis B，finite treatment,