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

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

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.

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