A Study to Evaluate the Safety, Tolerability of HH-003 Injection in Participants With Chronic Hepatitis B Virus Infection

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, placebo-controlled, multiple-ascending dose phase Ib study of HH-003 injection, which is a monoclonal antibody targeting Hepatitis B virus. This study aims to evaluate the safety, tolerability and pharmacokinetics of HH-003 injection in treatment-naive participants chronically infected with hepatitis B virus.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase Ib Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple-dose HH-003 Injection in Treatment Naïve Participants With HBeAg-positive Chronic HBV Infection

Conditions
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Chronic HBV Infection

Intervention / Treatment
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* Drug: HH-003 injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 45 years old Body weight ≥ 45 kg for men and ≥ 40 kg for women, and 18 kg/m^2≤BMI≤28 kg/m^2 Positive serum HBsAg or HBV DNA for at least 6 months,or previous liver biopsy results confirm the Hepatitis B HBeAg positive, and 2000 IU/mL<HBsAg<100,000 IU/mL Have not received interferon treatment before, and have not received nucleotide/nucleoside analogue treatment within 6 months prior to Screening Exclusion Criteria: Positive test for hepatitis C antibody (HCV-Ab), treponema pallidum antibody (TP-Ab), or anti-HIV antibody (HIV-Ab) Hemoglobin <100 g/L, platelets <100,000/mm^3 (100×10^9/L), absolute neutrophils count <1,500/mm^3 (1.5×10^9/L) Serum albumin <35 g/L, international normalized ratio (INR)>1.5; serum creatinine >115 μmol/L, Glomerular Filtration Rate (GFR) <70 mL/min/1.73m^2(calculated by Modification of Diet in Renal Disease (MDRD) formula); uric acid>540 μmol/L; triglyceride>3.5mmol/L Participants with a history of alcoholic liver disease, moderate or higher nonalcoholic fatty liver disease, autoimmune liver disease, Gilbert syndrome or other hereditary liver disease, drug-induced liver disease and other chronic liver diseases Participants with a history of progressive liver fibrosis (eg: liver cirrhosis diagnosed by liver histopathological examination, or esophagogastric varices diagnosed by endoscopy) Participants with confirmed or suspected decompensated HBV cirrhosis with complications of ascites, hepatic encephalopathy, gastroesophageal variceal bleeding, and Child-Pugh score of B C, or with primary liver cancer Alpha Fetoprotein (AFP) >50 ng/ml at screening or the suspected malignant liver mass indicated by imaging Any previous or current malignant neoplasms Breast-feeding or pregnant females Participants who are not suitable to participate in this trial per the Investigator's judgment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HH-003 Group<br> | Drug: HH-003 injection<br>* HH-003 injection is administrated via I.V. infusion<br>|
| Placebo Comparator: Placebo Group<br> | Drug: Placebo<br>* Placebo is administrated via I.V. infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events |  | From the first dose of study drug until Day 57 | 
| Peak concentration (Cmax) |  | From predose to Day 113 | 
| Area under the drug-time curve (AUC0-2W） |  | From predose to Day 113 | 
| Area under the drug-time curve (AUClast) |  | From predose to Day 113 | 
| Area under the drug-time curve (AUCinf) |  | From predose to Day 113 |