Study to Evaluate Safety and Efficacy of ASC42 Combined With ETV and PEG-IFN α-2a in Subjects With HBV

Study Overview
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Brief Summary
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This is a phase2, randomized, single-blind, placebo controlled and multi-center study in adults with chronic hepatitis B virus. The study is aimed at evaluating efficacy and safety of ASC42 in combination with entecavir and pegylated interferon α-2a in subjects with chronic hepatitis B virus.

Official Title
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A Phase II Multi-center, Randomized, Single-blind, Placebo-controlled to Evaluate Safety and Efficacy of ASC42 Tablets in Combination With Entecavir and Pegylated Interferon α-2a in Subjects With Chronic Hepatitis B Virus

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: ASC42 10mg
* Drug: ASC42 15mg
* Drug: ih PEG-IFN α-2a
* Drug: Entecavir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years old (including 18 and 65 years old); Chronic HBV infection confirmed by serological, etiological and clinical diagnosis (HBsAg positive for more than 6 months); HBV-DNA negative after nucleoside (acid) treatment; Laboratory test values meet the following requirements : Liver function : AST, ALT ≤ 3×ULN; serum total bilirubin≤2×ULN; direct bilirubin≤1.5×ULN; serum albumin≥35 g/L (blood collection is not within 2 weeks before transfusion of albumin); Hematology: white blood cell count>3.0×109/L, ANC>1.5×109/L; platelet>1×ULN; hemoglobin 120g/L. (No blood transfusion (including transfusion of red blood cells and platelets) and EPO, TPO, leukocyte-stimulating factor were required within 2 weeks before blood collection) ; Renal function: serum creatinine≤1×ULN; Thyroid function: TSH and T4 in normal range or thyroid function can be completely controlled ; Determination of serum immunoglobulin : IgM≤ULN; Coagulation function: International normalized ratio: INR≤1×ULN; Exclusion Criteria: Chronic HBV with unexplained portal hypertension; Subjects with liver cancer or serum AFP >1×ULN; Previously received FXR therapy;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Queue ASC42 10mg<br>ASC42 10mg, ih PEG-IFN α-2a and ETV for 12 weeks. | Drug: ASC42 10mg<br>* ASC42 10mg orally once daily;<br>Drug: ih PEG-IFN α-2a<br>* ih PEG-IFN α-2a 180μg subcutaneous injection once a week.<br>Drug: Entecavir<br>* Entecavir 0.5 mg orally once daily.<br>|
| Experimental: Queue ASC42 15mg<br>ASC42 15mg , ih PEG-IFN α-2a and ETV for 12 weeks. | Drug: ASC42 15mg<br>* ASC42 15mg orally once daily.<br>Drug: ih PEG-IFN α-2a<br>* ih PEG-IFN α-2a 180μg subcutaneous injection once a week.<br>Drug: Entecavir<br>* Entecavir 0.5 mg orally once daily.<br>|
| Placebo Comparator: Queue Placebo<br>Placebo, ih PEG-IFN α-2a and ETV for 12 weeks. | Drug: ih PEG-IFN α-2a<br>* ih PEG-IFN α-2a 180μg subcutaneous injection once a week.<br>Drug: Entecavir<br>* Entecavir 0.5 mg orally once daily.<br>Drug: Placebo<br>* Placebo orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum HBsAg change compared with baseline |  | Week 12 of intervention\Week 24 of follow-up | 
| Serum HBV pgRNA change compared with baseline |  | Week 12 of intervention\Week 24 of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum HBsAg change compared with baseline |  | Week 2, 4 ,8 of intervention\Week 4,12 of follow-up | 
| Serum HBV pgRNA change compared with baseline |  | Week 2, 4 ,8 of intervention\Week 4,12 of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Chronic, ASC42