A Study to Evaluate the Antiviral Activity and Safety of HH-003 in Chronic Hepatitis B Subjects With Low-level Viremia

Study Overview
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Brief Summary
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This is a multicenter, randomized, controlled Phase IIa study of HH-003 to evaluate the antiviral activity and safety in nucleos(t)ide analogues-treated chronic hepatitis B subjects with low-level viremia. HH-003 is a human monoclonal antibody targeting the pre-S1 domain of the HBV large envelope protein. It blocks engagement of preS1 with sodium taurocholate co-transporting polypeptide (NTCP), the cellular receptor for HBV.

Official Title
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A Multicenter, Randomized, Controlled Phase IIa Study to Evaluate the Antiviral Activity and Safety of HH-003 in Nucleos(t)Ide Analogues-treated Chronic Hepatitis B Subjects With Low-Level Viremia

Conditions
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Chronic HBV Infection

Intervention / Treatment
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* Drug: Nucleoside/nucleotide reverse transcriptase inhibitors (NrtIs)
* Drug: HH-003 and NrtIs
* Drug: HH-003, NrtIs and PEG-IFN-α


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form; Male or female aged from 18 to 60 years (inclusively); 18 kg/m^2≤BMI≤30 kg/m^2, body weight≥50 kg for men and ≥45 kg for women; Subjects who have chronic HBV infection greater than or equal to 6 months at screening; 10 IU/mL≤HBsAg≤3000 IU/mL; HBV DNA≤2000 IU/mL; ALT≤3×ULN; Subjects who have been on nucleoside reverse transcriptase inhibitors therapy for more than 1 year prior to screening. Exclusion Criteria: Females who are pregnant or lactating at screening; History of alcoholic liver disease, moderate fatty liver, autoimmune liver disease, other hereditary liver disease, drug-induced liver disease or other clinically significant chronic liver disease induced by non-HBV infection; History of cirrhosis at any time prior to or at time of screening, or having progressive liver fibrosis at screening ; History or evidence of hepatocellular carcinoma at any time prior to or at time of screening; Exclusionary laboratory results at screening: total bilirubin >2xULN or direct bilirubin >1.5xULN，hemoglobin <120 g/L for males or <110 g/L ro females，platelets count<100,000/mm^3 (100×10^9/L), and absolute neutrophils count <1,500/mm^3 (1.5×10^9/L).

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NrtIs<br> | Drug: Nucleoside/nucleotide reverse transcriptase inhibitors (NrtIs)<br>* Subjects will receive NrtIs therapy for 24 weeks.<br>|
| Experimental: HH-003+NrtIs<br> | Drug: HH-003 and NrtIs<br>* Subjects will receive HH-003 20 mg/kg intravenously Q2W and NrtIs therapy for 24 weeks.<br>|
| Experimental: HH-003+NrtIs+PEG-IFN-α<br> | Drug: HH-003, NrtIs and PEG-IFN-α<br>* Subjects will receive HH-003 20 mg/kg intravenously Q2W, NrtIs therapy and PEG-IFN-α 180μg SC QW for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with HBV DNA negativation |  | Week 24 | 
| Changes from baseline in serum HBsAg |  | From treatment start up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects achieving maintained virologic response (MVR) |  | From treatment start up to 48 weeks | 
| Duration of MVR |  | From treatment start up to 48 weeks | 
| Percentage of subjects with ALT normalization |  | From treatment start up to 48 weeks | 
| Changes from baseline in serum HBeAg in subjects with positive HBeAg |  | From treatment start up to 48 weeks |