A Study to Evaluate the Antiviral Activity and Safety of HH-003 Injection in Subjects With HBeAg-Negative Chronic Hepatitis B Treated With Nucleos(t)Ide Reverse Transcriptase Inhibitors

Study Overview
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Brief Summary
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This is a multicenter, randomized, controlled Phase IIa study of HH-003 injection, HH-003 injection is a monoclonal antibody targeting Hepatitis B virus. This study aims to evaluate the antiviral activity and safety in subjects with with HBeAg-negative Chronic Hepatitis B treated with nucleos(t)ide reverse transcriptase inhibitors.

Official Title
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A Multicenter, Randomized, Controlled Phase IIa Study to Evaluate the Antiviral Activity and Safety of HH-003 Injection in Subjects With HBeAg-Negative Chronic Hepatitis B Treated With Nucleos(t)Ide Reverse Transcriptase Inhibitors

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: NrtIs
* Drug: HH-003
* Drug: HH-003+NrtIs


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 65years (inclusively); 18 kg/m^2≤BMI≤32 kg/m^2, body weight≥45 kg for men and ≥40 kg for women; At screening, etiological, clinical, or pathological evidence indicates chronic hepatitis B virus infection for at least 6 months; and negative HBeAg for more than 6 months; 10 IU/mL≤HBsAg≤3000 IU/mL; HBV DNA≤20 IU/mL; ALT≤1×ULN; Participants who have been on the treatment of nucleos(t)ide reverse transcriptase inhibitors (limited to entecavir [ETV], tenofovir disoproxil fumarate [TDF], or tenofovir alafenamide fumarate [TAF]) for at least 3 years (as judged by the investigator) at screening. Exclusion Criteria: Females who are pregnant or lactating at screening; History of alcoholic liver disease, non-alcoholic steatohepatitis, autoimmune liver disease, other hereditary liver disease, drug-induced liver disease or other clinically significant chronic liver disease induced by non-HBV infection; History or presence of progressive liver fibrosis or cirrhosis, including but not limited to liver stiffness measurement [LSM] ≥ 9 kPa at screening, progressive liver fibrosis or cirrhosis (e.g., S ≥ 3 in GS score or METAVIR ≥ F3) by liver histopathology examination, according to the Consensus on the diagnosis and therapy of hepatic fibrosis [2019]; or the presence of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, or esophageal and gastric varices. History or presence of hepatocellular carcinoma, or alpha-fetoprotein (AFP) ≥ 50 ng/mL at screening; or suspicion of hepatocellular carcinoma indicated by liver ultrasound, CT, or MRI. Use of antiviral therapy with interferon within 1 year prior to screening Any of the following lab test 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), Serum albumin < 35 g/L; international normalized ratio (INR) of prothrombin time > 1.3; or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NrtIs<br> | Drug: NrtIs<br>* Subjects will receive NrtIs therapy for 24 weeks.<br>|
| Experimental: HH-003<br> | Drug: HH-003<br>* Subjects will receive HH-003 20 mg/kg intravenously Q2W for 24 weeks.<br>|
| Experimental: HH-003+NrtIs<br> | Drug: HH-003+NrtIs<br>* Subjects will receive HH-003 20 mg/kg intravenously Q2W for 24 weeks. Subjects will receive NrtIs therapy for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving sustained viral response |  | From baseline to Week 24 | 
| Changes from baseline in serum HBsAg levels |  | From treatment start to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with undetectable HBV DNA in those with positive HBV DNA at baseline |  | From treatment start to Week 24 | 
| Proportion of participants achieving sustained viral response |  | From baseline to Week 48 | 
| Duration of sustained viral response |  | From treatment start to Week 48 | 
| Changes from baseline in serum HBsAg levels |  | From treatment start up to Week 48 | 
| Proportion of participants with HBV pgRNA negativation in those with positive HBV pgRNA at baseline |  | From baseline to Week 24 | 
| Proportion of participants with normal ALT levels |  | From treatment start to Week 48 |