A Study Evaluating AHB-137 in Healthy Participants and Participants With Chronic Hepatitis B

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of AHB-137 subcutaneous injection in healthy volunteers and in chronic hepatitis B (CHB) patients after single and multiple doses. In addition, the study will evaluate the antiviral efficacy of AHB-137 in CHB patients following a multiple dosing regimen.

Inclusion Criteria:Healthy participants are required to meet all the following inclusion criteria in order to be enrolled in the study:18-65 years old male or female.Body Mass Index (BMI) between 19 to 35 kg/m2 (inclusive) and body weight equal to or over 45 kg.Healthy female volunteers cannot be pregnant at the time of recruiting and during the study. Healthy female volunteers with childbearing potential must remain abstinent or use two methods of contraception with their partner, one of which must be a barrier method (E.g. condom), for the duration of the study and for at least 3 months after the last dose of study-drug.For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.Participants' COVID-19 PCR test should be negative during screening.Participants' COVID-19 Rapid Antigen Test (RAT) should be negative at check-in.CHB patients are required to meet all the following inclusion criteria in order to be enrolled in the study:Have given written informed consent (signed and dated) and any authorizations required by local law and is able to comply with all study requirements.Age 18 to 65 years old.ALT < 5 ULN.CHB patients who have documented chronic HBV infection equal to or above 6 months prior to screening. Otherwise, CHB patients need to be HBsAg positive and IgM HBcAb negative.Female patients cannot be pregnant at the time of recruiting and during the study. Healthy female volunteers with childbearing potential must remain abstinent or use two methods of contraception with their partner, one of which must be a barrier method (E.g. condom), for the duration of the study and for at least 3 months after the last dose of study-drug. For male patients: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.Participants receiving stable nucletos(t)ide analogue (NA) therapy were expected to continue NA therapy during the trial; participants not receiving NA therapy at the time of trail entry were expected to continue without NA during the trail.COVID-19 PCR test should be negative during screening.COVID-19 RAT test should be negative at check-in.Exclusion Criteria:Healthy participants are required to not meet any of the exclusion criteria in order to be enrolled in the study:Pregnant (positive pregnancy test) or lactating women. Male participants without using proper contraceptives (e.g. condom) with partners who are pregnant or lactating.History or symptoms of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis.Personal history of congenital long QT syndrome or family history of sudden cardiac death.Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable).Any clinically significant concomitant diseases or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study.Clinically relevant electrocardiogram (ECG) abnormalities on screening ECG.ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement.Creatinine clearance (CrCl) cutoff = 80 ml/min (using the Cockcroft-Gault formula).Positive test at screening of any of the following: hepatitis A (HAV IgM Ab), hepatitis B (HBsAg), hepatitis C (HCV RNA or HCV Ab), human immunodeficiency virus 1 and 2 (HIV Ab), or TP-Ab.Any other clinically significant abnormalities in laboratory test results at screening. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility.History of bleeding diathesis or coagulopathy.CHB patients are required to not meet any of the exclusion criteria in order to be enrolled in the study:History of liver cirrhosis and/or evidence of cirrhosis as determined by any 1 of the following:Liver biopsy (i.e., Metavir Score F4) within 2 years of screening, orFibroScan > 12 KPa, within 12 months of screening, orAST-to-Platelet Index (APRI) > 2 and FibroSure result > 0.7 within 12 months of screening.For patients without a test for cirrhosis in the above timeframes, FibroScan, or APRI and FibroSure, may be performed during the screening period to rule out cirrhosis History of liver failure as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices.History of liver disease other than hepatitis B.Co-infection with TP, HCV, HIV, or hepatitis D virus (HDV).Body mass index >35 kg/m2 .History or suspected presence of vasculitis .Diagnosed hepatocellular carcinoma or suspected hepatocellular carcinoma as evidenced by screening alpha-fetoprotein ≥200 ng/mL. If the screening alpha-fetoprotein is ≥50 ng/mL and <200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization.Clinically relevant electrocardiogram (ECG) abnormalities on screening ECG.Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a patient unsuitable for inclusion.ALT or Aspartate-amino-transferase (AST) > 5 x ULNTotal bilirubin >1.5 x ULNSerum albumin <3.5 g/dLInternational normalized ratio >1.2Platelet count <140 k/mm3Hemoglobin <12.0 g/dL for males and <11.0 g/dL for femalesWhite blood cell count <3.0 k/mm3Serum creatinine >1.1 x ULNUrine protein/creatinine ratio ≥0.2 mg/mg. In the event of a ratio above this threshold, eligibility may be confirmed by a quantitative total urine protein measurement of <150 mg/24 hourPositive test (including trace) for blood on urinalysis. In the event of a positive test, eligibility may be confirmed with urine microscopy showing <5 red blood cells per high power fieldClinically significant abnormalities aside from chronic HBV infection in medical history (e.g., previous acute coronary syndrome within 6 months of screening, major surgery within 3 months of screening, uncontrolled diabetes) or physical examination.History of bleeding diathesis or coagulopathy.History of extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis, polyarteritis nodosa) .Active infection other than HBV, requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1.