Hepatitis B, Chronic
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of AHB-171 in participants with chronic hepatitis B (CHB). Study advancement to subsequent parts/cohorts will require satisfactory interim reviews of available cumulative safety data by the Safety Review Committees (SRC), using the safety criteria and review procedures described in the protocol.
Interventions
DRUGAHB-171
Injection
DRUGPlacebo matching [Investigational Product]
Injection
Oral administration
Sponsors
AusperBio Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants, aged 18-65 years old (inclusive) * Body Mass Index between 19 to 35 kg/m2 (inclusive) * Body weight \> or = 45 kg. * Documented HBV infection for ≥6 months prior to randomization. * For Parts A and B, on stable approved NA monotherapy for at least 6 months prior to randomization. * For Part C and D only, not on any NA monotherapy for at least 6 months prior to randomization. * Screening electrocardiogram (ECG) without clinically significant abnormalities * Females of childbearing potential must not be breastfeeding, must have a negative serum pregnancy test at Screening, and a negative urine/serum pregnancy test before dosing (unless permanently sterile or \>2 years postmenopausal). * Males and females of childbearing potential must agree to use protocol specified reliable contraception throughout the study. * Screening HBV DNA, HBsAg and ALT must meet prespecified requirements.
Exclusion criteria
* Significant medical conditions other than chronic HBV (e.g. recent heart issues, unstable cardiac disease, uncontrolled diabetes, bleeding disorders, prior organ transplant). * Other clinically significant liver diseases (e.g. hepatitis from other causes, autoimmune or alcoholic liver disease, prior liver failure). * History of suspected or confirmed cirrhosis (based on FibroScan® or biopsy). * Current, past, or suspected liver cancer, or elevated alpha-fetoprotein (AFP) ≥ 20 ng/mL. * HBV-related extrahepatic diseases (e.g. kidney or vascular conditions). * Severe infection (other than chronic HBV infection) within 1 month before randomization requiring intravenous treatment. * Active infections: human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV) or syphilis (exceptions if RNA negative). * Abnormal lab results (e.g. low albumin, reduced kidney function, abnormal INR, low platelets, high bilirubin, abnormal blood counts, significant proteinuria). * History or signs of vasculitis or related autoimmune diseases. * Malignancy within 5 years (except non-melanoma skin cancer). * Allergy to study drug components. * Recent major surgery/trauma (within 3 months) or planned surgery during study. * Alcohol or substance abuse affecting compliance. * Pregnancy, breastfeeding, or unwillingness to follow reproductive restrictions. * Participation in another clinical trial or recent investigational product use. * Prior treatment with any antisense oligonucleotide or small interfering RNA therapies. * Recent or ongoing use of immunosuppressive/biologic therapies, certain vaccines, bulevirtide, or unapproved herbal remedies. * Need for long-term anticoagulants/antiplatelet drugs (unless safely stopped). * Any other condition making the participant unsuitable (per investigator).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) [Safety and Tolerability] | Up to 72 weeks | — |
| The plasma pharmacokinetic (PK) profile of AHB-171 and metabolites: the maximum observed plasma concentration (Cmax) of AHB-171. | Up to 72 weeks | — |
| The plasma pharmacokinetic (PK) profile of AHB-171 and metabolites: the area under the concentration-time curve extrapolated to infinity (AUCinf ) of AHB-171 | Up to 72 weeks | — |
| Incidence of clinically significant changes in Vital Signs [Safety and Tolerability] | Up to 72 weeks | Vital signs include body temperature, pulse rate, respiratory rate, and blood pressure |
| Incidence of clinically significant changes in cardiac parameters [Safety and Tolerability] | Up to 72 weeks | 12-lead electrocardiogram (ECG) abnormalities will be reported, with parameters evaluated including PR interval, QRS duration, QT/QTc interval. |
| Incidence of laboratory abnormalities [Safety and Tolerability] | Up to 72 weeks | — |
| The plasma pharmacokinetic (PK) profile of AHB-171 and metabolites: area under the curve from the time of dosing to the last measurable concentration (AUClast) of AHB-171 | Up to 72 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute serum HBsAg (Hepatitis B surface antigen) and change from baseline across all evaluated timepoints in the study | Up to 72 weeks | — |
| Absolute serum HBV (Hepatitis B virus) DNA and change from baseline across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Absolute serum HBeAb (Hepatitis B e Antibody) and change from baseline across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Proportion of participants achieving pre-specified HBsAg reduction levels or absolute thresholds across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Proportion of participants achieving HBsAg < or ≥ LOD (limit of detection) and/or HBV DNA < or ≥ LLOQ (lower limit of quantitation) across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Proportion of participants achieving pre-specified HBV DNA levels or absolute thresholds across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Time to achieving pre-specified HBsAg levels or absolute thresholds across all evaluated timepoints in the study | Up to 72 weeks | — |
| Change from baseline in alanine aminotransferase (ALT) levels | Up to 72 weeks | — |
| Proportion of participants with ALT normalization among those with elevated ALT at baseline across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Proportion of participants achieving anti-HBs seroconversion across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Proportion of participants experiencing virologic relapse. | Up to 72 weeks | Virologic relapse is defined as HBV DNA meeting a protocol-specified threshold value at 2 consecutive visits |
| Time to participants experiencing virologic relapse. | Up to 72 weeks | Virologic relapse is defined as HBV DNA meeting a protocol-specified threshold value at 2 consecutive visits |
| Proportion of participants with treatment emergent AEs (TEAEs), serious AEs (SAEs), or discontinuation due to AEs. | Up to 72 weeks | — |
| Proportion of participants with anti-drug antibodies (ADA) to AHB-171. | Up to 72 weeks | — |
| ADA titers in participants with ADA to AHB-171 across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Plasma PK parameters AUC of AHB-171 and metabolites. | Up to 72 weeks | — |
| Plasma PK parameter Cmax of AHB-171 and metabolites. | Up to 72 weeks | — |
| Plasma PK parameter Time to Peak Concentration (tmax) of AHB-171 and metabolites. | Up to 72 weeks | — |
| Plasma PK parameter apparent clearance (CL [clearance]/F [Bioavailability]) of AHB-171 and metabolites. | Up to 72 weeks | — |
| Urine PK parameter cumulative amount excreted (Ae) of AHB-171 and metabolites. | Up to 72 weeks | — |
| Urine PK parameter renal clearance (CLr) of AHB-171 and metabolites. | Up to 72 weeks | — |
| Absolute serum HBV ribonucleic acid (RNA) and change from baseline across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Absolute serum HBcrAg (Hepatitis B core-related antigen) and change from baseline across all evaluated timepoints in the study | Up to 72 weeks | — |
| Absolute serum HBeAg (Hepatitis B e antigen) and change from baseline across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Proportion of participants with hs-HBsAg (high-sensitivity HBsAg) <LLOQ across all evaluated timepoints in the study. | Up to 72 weeks | — |
| Absolute serum HBsAb (Hepatitis B surface Antibody) and change from baseline across all evaluated timepoints in the study. | Time Frame: Up to 72 weeks | — |
| Time to first hs-HBsAg <LLOQ, assessed at scheduled visits | Up to 72 weeks | — |
Countries
Hong Kong, New Zealand
Contacts
CONTACTDebbie Liao
Outcome results
None listed