Hepatitis B, Chronic
Conditions
Keywords
Hepatitis, Chronic Hepatitis, Chronic Hepatitis B, Hepatitis B, Hepatitis B, Chronic, Hepatitis B Virus, hepatitis B virus e-antigen, AHB-137, Nucleos(t)ide analogue, Nucleos(t)ide analog, Antisense Oligonucleotide, Blood-Borne Infections, Communicable Diseases, Infections, DNA Virus Infections, Virus Diseases, Hepatitis, Viral, Human, Liver Diseases, Digestive System Diseases, Chronic Disease, Disease Attributes, Pathologic Processes, Pathological Conditions, Signs and Symptoms
Brief summary
This study is a randomized, open-label, multicenter phase 2 clinical trial to evaluate the efficacy and safety of AHB-137 injection in participants with CHB treated with Nucleos(t)ide Analogue (NAs).
Interventions
DRUGAHB-137
Subcutaneous injection
Sponsors
AusperBio Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply: 1. Adults ≥18 years of age and up to 65 years of age (inclusive) at Screening who are able to provide informed consent, comply with study procedures, and agree to discontinue nucleos(t)ide analog (NA) therapy if protocol-defined discontinuation criteria are met. 2. Body mass index (BMI) ≤35 kg/m². 3. Documented chronic hepatitis B virus (HBV) infection for ≥6 months prior to randomization, defined by hepatitis B surface antigen (HBsAg) positivity or detectable HBV DNA. 4. Receiving stable, approved nucleos(t)ide analog (NA) monotherapy for ≥6 months prior to randomization. 5. HBV DNA meeting protocol-specified virologic criteria at Screening. 6. Hepatitis B surface antigen (HBsAg) level meeting protocol-specified virologic criteria at Screening. 7. Alanine aminotransferase (ALT) meeting protocol-specified criteria at Screening. 8. Screening electrocardiogram (ECG) without clinically significant abnormalities and with a Fridericia-corrected QT interval (QTcF) ≤450 msec for males or ≤470 msec for females. 9. Females of childbearing potential must not be breastfeeding and must have a negative serum pregnancy test at Screening and a negative urine pregnancy test prior to first dose. 10. Males and female participants of childbearing potential must agree to use protocol-specified effective contraception during the dosing period and for ≥6 months after the last dose of AHB-137.
Exclusion criteria
Participants will be excluded from the study if any of the following criteria apply: 1. Clinically significant disease other than chronic hepatitis B virus (HBV) infection. 2. Concomitant clinically significant liver disease. 3. Any severe infection (other than chronic HBV infection) within 1 month prior to randomization. 4. History of immune thrombocytopenia. 5. Current suspected liver cirrhosis and/or evidence of cirrhosis by protocol-specified criteria for FibroScan® or equivalent imaging modality (e.g., ultrasound elastography); historical FibroScan® (or equivalent) results with documentation within 6 months from screening is acceptable. 6. History of liver cirrhosis defined by liver biopsy or by FibroScan® or equivalent imaging modality using protocol-specified criteria. 7. Prior history of, current diagnosis of, or suspected hepatocellular carcinoma (HCC), or alpha-fetoprotein (AFP) ≥20 ng/mL at Screening. 8. History of extrahepatic diseases potentially associated with HBV infection. 9. Laboratory evidence of active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV), or active syphilis. Participants with positive HCV or HDV serology and documented negative HCV RNA or HDV RNA, respectively, are eligible. 10. Protocol-specified abnormal laboratory values at Screening. 11. History of vasculitis or presence of signs or symptoms suggestive of vasculitis, or history or presence of diseases associated with vasculitis. 12. History of malignancy within 5 years prior to Screening, except for adequately treated non-melanoma skin cancer. Participants currently undergoing evaluation for potential malignancy are excluded. 13. History of hypersensitivity or allergy to any component of the investigational product (IP). 14. Major trauma or major surgery within 3 months prior to Screening, or planned surgery during the study period unless eligibility is confirmed by the Medical Monitor. 15. Current alcohol or substance abuse judged by the Investigator to potentially interfere with participant compliance. 16. Female participants who are pregnant, breastfeeding, planning pregnancy during the study, or unwilling to refrain from egg donation and/or in vitro fertilization during the study. 17. Participation in another clinical trial or receipt of any investigational product prior to first dose in this study within: 1. Five half-lives (if known) or twice the duration of biological effect (if known), whichever is longer, or 2. Six months, if neither half-life nor duration of effect is known 18. Prior treatment with antisense oligonucleotides (ASOs) or small interfering RNA (siRNA)-based therapies. 19. Any of the following prior or concomitant therapies: 1. Prolonged use of immunomodulators (e.g., corticosteroids, methotrexate), cytotoxic drugs, or biologics (e.g., monoclonal antibodies) within 6 months prior to first IP administration, except for short-term treatment (≤2 weeks) or topical/inhaled corticosteroids 2. Interferon therapy within 12 months prior to first dose 3. Vaccination within 1 month prior to Screening, except for influenza or SARS-CoV-2 (COVID-19) vaccination or booster 4. Current treatment with bulevirtide 20. Requirement for long-term regular use of anticoagulants (e.g., warfarin, factor Xa inhibitors) or antiplatelet agents (e.g., clopidogrel or regular aspirin), except for low-dose aspirin. 21. Any other condition or circumstance that, in the Investigator's judgment, would make the participant unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants with persistent HBsAg < limit of detection (LOD) and HBV DNA < lower limit of quantification (LLOQ) | 24 Weeks post AHB-137 treatment (Week 48) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with HBsAg < LOD and HBV DNA < LLOQ | Off-treatment follow-up (Week 48 to 72) | — |
| Proportion of participants with HBsAg < LOD | Week 72 | — |
| Proportion of participants with HBV DNA < LLOQ | From baseline through Week 72 | — |
| Proportion of participants with protocol-defined virologic response for HBsAg and HBV DNA post AHB-137 treatment | 24 weeks post AHB-137 treatment | — |
| Proportion of participants with protocol-defined virologic response for HBsAg and HBV DNA at weeks 48 and 72 | 24 weeks post AHB-137 treatment and at Week 72 | — |
| Proportion of participants with protocol-defined virologic response for HBsAg and HBV DNA | From baseline through end of study (Week 72) | — |
| Proportion of participants with HBsAg < or ≥ LOD (0.05 IU/mL) and/or HBV DNA < or ≥ LLOQ | From baseline through end of study (Week 72) | — |
| Proportion of participants with highly sensitive HBsAg < LOD (0.005 IU/mL) | From baseline through end of study (Week 72) | — |
| Proportion of participants with protocol-defined levels of HBsAg | From baseline through end of study (Week 72) | — |
| Proportion of participants that meet nucleos(t)ide analog (NA) discontinuation criteria | Week 48 | — |
| Categorical change from baseline in HBsAg levels, defined as reductions of ≥0.5, ≥1.0, ≥1.5, ≥2.0, or ≥3.0 log₁₀ IU/mL, assessed at each scheduled study visit | From baseline through end of study (Week 72) | — |
| Proportion of participants with anti-HBs seroconversion (with hepatitis B surface antibody [HBsAb] > 10 IU/L) | Weeks 24, 48, and 72 | — |
| Quantitative hepatitis B virologic and serologic markers over time | From baseline through end of study (Week 72) | Actual values and change from baseline over time in available quantitative hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B virus (HBV) DNA, HBV ribonucleic acid (RNA), hepatitis B core-related antigen (HBcrAg), hepatitis B e antibody (HBeAb), and qualitative and/or quantitative hepatitis B e antigen (HBeAg), summarized descriptively. |
| Proportion of participants who experience virologic relapse | From baseline through Week 72 | — |
| Time from nucleos(t)ide analog (NA) therapy discontinuation to virologic relapse | From NA therapy discontinuation (Week 48) through end of follow-up (Week 72) | — |
| Change from baseline in alanine aminotransferase (ALT) | From baseline through end of study (Week 72) | — |
| Proportion of participants with baseline ALT above the upper limit of normal (ULN) who achieve ALT normalization | From baseline through end of study (Week 72) | — |
| Proportion of patients with drug-resistant mutations | From baseline through end of study (Week 72) | — |
| Proportion of participants with treatment-emergent adverse events (TEAEs) | From first dose (Day 1) through end of study (Week 72) | Proportion of participants who experience treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events leading to discontinuation of study treatment. |
| Proportion of participants with detectable anti-drug antibody (ADA) to AHB-137 and corresponding ADA titers | From baseline through end of study (Week 72) | — |
| Area under the plasma concentration-time curve (AUC) of AHB-137 | From first dose (Day 1) through end of pharmacokinetic sampling (Week 48) | — |
| Concentration at the end of the dosing interval (Ct) of AHB-137 | From first dose (Day 1) through end of pharmacokinetic sampling (Week 48) | — |
| Maximum observed plasma concentration (Cmax) of AHB-137 | From first dose (Day 1) through end of pharmacokinetic sampling (Week 48) | — |
| Time to maximum observed plasma concentration (Tmax) of AHB-137 | From first dose (Day 1) through end of pharmacokinetic sampling (Week 48) | — |
| Apparent plasma clearance (CL/F) of AHB-137 | From first dose (Day 1) through end of pharmacokinetic sampling (Week 48) | — |
| Area Under the Plasma Concentration-Time Curve (AUC) of AHB-137 | From first dose (Day 1) through end of study (Week 72) | — |
| Plasma Concentration of AHB-137 at the End of the Dosing Interval (Cτ) | From first dose (Day 1) through end of study (Week 72) | — |
| Maximum Observed Plasma Concentration (Cmax) of AHB-137 | From first dose (Day 1) through end of study (Week 72) | — |
| Time to Maximum Observed Plasma Concentration (Tmax) of AHB-137 | From first dose (Day 1) through end of study (Week 72) | — |
| Apparent Plasma Clearance (CL/F) of AHB-137 | From first dose (Day 1) through end of study (Week 72) | — |
Countries
Canada, France, Italy, Spain, United Kingdom, United States
Contacts
CONTACTMaggie Davis
STUDY_DIRECTORAudrey Lau, MD, PhD
AusperBio Therapeutics Inc.
Outcome results
None listed