A Phase II Study of Hepalatide in Subjects With Chronic Hepatitis B

Study Overview
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Brief Summary
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A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-effect Relationship Study of Hepalatide for Injection Combined with Pegylated Interferon in Subjects with Chronic Hepatitis B

Detailed Description
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The study is a 4-arm parallel design, randomized, double-blind, placebo-controlled, multicenter, dose-effect relationship, phase II clinical trial. The study is designed to assess efficacy and safety of 3 Doses of hepalatide in Combination with Pegylated Interferon Compared to Pegylated Interferon Alone in patients with Chronic Hepatitis B .Subjects will be randomly assigned to the 2.1mg, 4.2mg, and 6.3mg dose groups , 32 subjects in each group . The subjects in each dose group will be randomly and double-blindly administered the corresponding dose of trial drug or placebo in a ratio of 3:1. The subjects in each dose group who received placebo treatment combine as the placebo group. All subjects will receive Pegylated Interferon treatment for 28 weeks as the basic treatment,trial drug or placebo treatment for 24 weeks continuously , followed by a safety follow-up for 4 weeks.

Official Title
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A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-effect Relationship Study of Hepalatide for Injection Combined With Pegylated Interferon in Subjects With Chronic Hepatitis B

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Hepalatide 2.1mg
* Drug: Hepalatide 4.2mg
* Drug: Hepalatide 6.3mg
* Drug: placebo 2.1mg
* Drug: placebo 4.2mg
* Drug: placebo 6.3mg
* Drug: Pegylated Interferon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 60 years inclusively at the time of signing Informed Consent Form. HBsAg or/and HBV DNA Positive for at least 6 months before Screening. Subjects did not receive interferon treatment and did not receive nucleotide/nucleoside analogue within 6 months HBeAg positive or negative HBV DNA≥20,000 IU/ml (HBeAg positive) or HBV DNA≥2,000 IU/ml (HBeAg negative) 2×ULN ≤ALT≤10×ULN Serum total bilirubin<2×ULN Subjects had no history of decompensated liver disease（Ascites, jaundice, hepatic encephalopathy, varicose hemorrhage）, serious heart disease (including unstable or uncontrolled heart disease within 6 months),serious mental illness (especially depression),organ transplantation .subjects have no uncontrolled epilepsy, mental illness, diabetes and hypertension,no autoimmune disease, immune related extrahepatic manifestations (vasculitis, purpura, nodular arteritis, peripheral neuropathy and glomerulonephritis), thyroid disease, malignant tumor, immunosuppressive therapy; no basic diseases and other serious diseases such as serious infection, retinal disease, heart failure and chronic obstructive pulmonary disease; no alcohol and drug abuse. Subjects must agree to use a highly effective contraception for 2 years , female subjects are not pregnant or breastfeeding Subjects did not donate blood or as clinical trial subjects within 3 months before screening Subjects have good compliance with the protocol Subjects understood and agreed to sign the informed consent form. Exclusion Criteria: Decompensated liver disease: direct bilirubin > 1.2 × ULN, Prothrombin time > 1.2 × ULN, serum albumin < 35 g / L Severe liver fibrosis or cirrhosis: METAVIR score of liver biopsy is 4 points; or or Child-Pugh score> 7 Hemocytopenia: neutrophil < 1 × 10^9 / L, platelet < 50 × 10^9 / L, hemoglobin < 100g / L (female) or hemoglobin < 110g / L (male) points HAV,HCV,HDV,HEV or HIV infection Pegylated interferon therapy is contraindicated Allergic to interferon, Such as severe depression, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction and so on severe retinopathy or eye disease(Eye diseases due to high blood pressure or diabetes, CMV retinitis, macular degeneration) Positive for anti-HBV Pre-S1 antibody. Hamilton Depression Scale (HAMD, 17 items) score > 17 points Female subjects pregnancy test positive 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hepalatide 2.1mg+Pegylated Interferon<br>Hepalatide 2.1mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks. PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks | Drug: Hepalatide 2.1mg<br>* 2.1 mg/day subcutaneously (s.c.) for 24 week<br>* Other names: L47;Drug: Pegylated Interferon<br>* 180 ug/week subcutaneously (s.c.) for 28 week<br>* Other names: Pegasys;|
| Experimental: Hepalatide 4.2mg+Pegylated Interferon<br>Hepalatide 4.2mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks. PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks | Drug: Hepalatide 4.2mg<br>* 4.2mg/day subcutaneously (s.c.) for 24 week<br>* Other names: L47;Drug: Pegylated Interferon<br>* 180 ug/week subcutaneously (s.c.) for 28 week<br>* Other names: Pegasys;|
| Experimental: Hepalatide 6.3mg+Pegylated Interferon<br>Hepalatide 6.3mg s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks. PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks | Drug: Hepalatide 6.3mg<br>* 6.3mg/day subcutaneously (s.c.) for 24 week<br>* Other names: L47;Drug: Pegylated Interferon<br>* 180 ug/week subcutaneously (s.c.) for 28 week<br>* Other names: Pegasys;|
| Active Comparator: placebo+Pegylated Interferon<br>Hepalatide placebo s.c., q.d., treatment continued for 24 weeks, follow up 4 weeks. PEG-IFNalpha, s.c., q.w.,treatment continued for 48 weeks | Drug: placebo 2.1mg<br>* 2.1 mg/day subcutaneously (s.c.) for 24 week<br>Drug: placebo 4.2mg<br>* 4.2 mg/day subcutaneously (s.c.) for 24 week<br>Drug: placebo 6.3mg<br>* 6.3 mg/day subcutaneously (s.c.) for 24 week<br>Drug: Pegylated Interferon<br>* 180 ug/week subcutaneously (s.c.) for 28 week<br>* Other names: Pegasys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| initial virological response | HBV DNA<20 IU/ml | 24weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV DNA down from baseline | HBV DNA down from baseline log10 | 24weeks |