Study of AHB-171 in Chronic Hepatitis B Participants

Official title

A Phase 1 Study in Chronic Hepatitis B Participants to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AHB-171

Overview

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

• Drug AHB-171
  Injection
• Drug Placebo matching [Investigational Product]
  Injection
• Drug Nucleos(t)ide Analogue (NA)
  Oral administration

Primary outcome measures

• Incidence of Adverse Events (AEs) [Safety and Tolerability] [Time frame: Up to 72 weeks]
• The plasma pharmacokinetic (PK) profile of AHB-171 and metabolites: the maximum observed plasma concentration (Cmax) of AHB-171. [Time frame: 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 [Time frame: Up to 72 weeks]
• Incidence of clinically significant changes in Vital Signs [Safety and Tolerability] [Time frame: Up to 72 weeks]
• Incidence of clinically significant changes in cardiac parameters [Safety and Tolerability] [Time frame: Up to 72 weeks]
• Incidence of laboratory abnormalities [Safety and Tolerability] [Time frame: 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 [Time frame: Up to 72 weeks]

Secondary outcome measures (12)

• Absolute serum HBsAg (Hepatitis B surface antigen) and change from baseline across all evaluated timepoints in the study [Time frame: Up to 72 weeks]
• Absolute serum HBV (Hepatitis B virus) DNA and change from baseline across all evaluated timepoints in the study. [Time frame: Up to 72 weeks]
• Absolute serum HBeAb (Hepatitis B e Antibody) and change from baseline across all evaluated timepoints in the study. [Time frame: Up to 72 weeks]
• Proportion of participants achieving pre-specified HBsAg reduction levels or absolute thresholds across all evaluated timepoints in the study. [Time frame: 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. [Time frame: Up to 72 weeks]
• Proportion of participants achieving pre-specified HBV DNA levels or absolute thresholds across all evaluated timepoints in the study. [Time frame: Up to 72 weeks]
• Time to achieving pre-specified HBsAg levels or absolute thresholds across all evaluated timepoints in the study [Time frame: Up to 72 weeks]
• Change from baseline in alanine aminotransferase (ALT) levels [Time frame: Up to 72 weeks]
• Proportion of participants with ALT normalization among those with elevated ALT at baseline across all evaluated timepoints in the study. [Time frame: Up to 72 weeks]
• Proportion of participants achieving anti-HBs seroconversion across all evaluated timepoints in the study. [Time frame: Up to 72 weeks]
• Proportion of participants experiencing virologic relapse. [Time frame: Up to 72 weeks]
• Time to participants experiencing virologic relapse. [Time frame: Up to 72 weeks]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Hong Kong · 1 center

• Queen Mary Hospital — Hong Kong

New Zealand · 1 center

• New Zealand Clinical Research — Grafton

Identifiers

NCT: NCT07617194 · AB-17-8001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗