Chronic Hepatitis B Infection
Conditions
Keywords
Hepatitis B, Chronic
Brief summary
The goal of this clinical trial is to evaluate the safety, tolerability, immunogenicity and Pharmacokinetics (PK) characteristics of AHB-171 Injection in healthy participants (Part A) and participants with chronic hepatitis B (CHB, Part B), and assess its preliminary efficacy in CHB participants.
Interventions
AHB-171 Injection is adminstrated via subcutaneous injection
DRUGPlacebo
Placebo is admistrated via subcutaneous injection
Oral administration
Sponsors
Ausper Biopharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Participants: * Male or female participants, aged 18-55 years old (inclusive); * Body mass index between 18.0 and 28.0 kg/m\^2 (inclusive); * Laboratory safety tests during the screening period, 12-lead electrocardiogram (ECG), abdominal ultrasound, thyroid ultrasound, chest anteroposterior position, etc., are assessed by the investigatoras normal or abnormal without clinical significance; * Female participants of childbearing potential must not be pregnant or lactating, must have a negative pregnancy test at screening, and must agree to use effective contraceptive methods and refrain from donating eggs from screening until 6 months after the last dose of the study drug. * Male participants must agree to use highly effective contraceptive methods (to ensure effective contraception for their female partners of childbearing potential) and refrain from donating sperm from screening until 6 months after the last dose of the study drug. Liver and kidney function tests meet the requirements at the time of screening. * CHB Participants: * Male or female participants, aged 18-65 years old (inclusive); * Body mass index between 18.0 and 32.0 kg/m\^2 (inclusive); * Participants who take effective contraceptive measures as required; * HBsAg \> 100 IU/mL and ≤ 3000 IU/mL, and HBV DNA \< 100 IU/mL at screening. * Have received stable treatment with NA for at least 6 months and stable on the same NA for at least 3 months before screening.
Exclusion criteria
* Healthy Participants: * Currently participating in another study, or within 5 half-lives/3 months of the last dose of a previous investigational product. * Presence diseases (cardiovascular, neurological, renal, immunological, metabolic, etc.) or malignant tumors.- Major surgery or severe trauma within the past 6 months. * Acute infection (e.g., influenza, gastroenteritis) within 14 days; vaccination within 28 days prior to screening. * Allergy to any investigational drug component. * Heavy Smoking (\> 5 cigarettes/day); history of drug/alcohol abuse; consumption of caffeine or alcohol within 48 hours before dosing. * Blood donation/loss ≥400 mL or transfusion within 12 weeks, or plan to donate during study. * Abdominal skin issues that may affect drug injection/observation. * Positive for HBV, HCV, HIV, or syphilis. * Clinically significant ECG abnormality or TdP risk factors. * Any condition judged unsuitable by investigator. * CHB Participants: * Currently participating in another study, or within 5 half-lives/3 months of the last dose of a previous investigational product. * Presence of ascites, gastrointestinal bleeding, hepatic encephalopathy, or varices. * History or suspicion of hepatocellular carcinoma (HCC); AFP \> 50 ng/mL. * Diagnosed or Suspected cirrhosis within 12 months. * History of transplantation, autoimmune diseases, or severe systemic diseases (besides chronic HBV). * Use of ASO, siRNA (oligonucleotide therapies), or interferon within 12 months. * Major injury/surgery within 6 months, planned surgery during study, or acute infection within 14 days. * Allergy to any investigational drug component. * Blood donation/loss ≥400 mL or transfusion within 12 weeks, or plan to donate during study. * Abdominal skin issues that may affect drug injection/observation. * Key laboratory result not suitable for clinical trial. * HIV, HCV, or active syphilis infection; uncured hepatitis A, D, or E. * Clinically significant ECG abnormality or TdP risk factors. * Any condition judged unsuitable by investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A & Part B Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Severity of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Change from baseline in laboratory tests | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Change from baseline in physical examinations | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Change from baseline in vital signs | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Change from baseline in electrocardiograms (ECGs) | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Part A:Plasma Cmax of AHB-171 | Up to Day 8 |
| Part A:Plasma Tmax of AHB-171 | Up to Day 8 |
| Part A Plasma AUC of AHB-171 | Up to Day 8 |
| Part A Plasma t1/2 of AHB-171 | Up to Day 8 |
| Proportion of participants with clinically significant abnormalities in laboratory tests | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Proportion of participants with clinically significant abnormalities in electrocardiograms (ECGs) | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Proportion of participants with physical examinations | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
| Proportion of participants with other vital signs | PartA:Up to 16 weeks, PartB: Up to 48 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Part A & Part B:Fraction excreted in urine in percentage for AHB-171 | Up to Day 3 in Part A; Up to Day 30 in Part B |
| Part A & Part B:Amount excreted in urine for AHB-171 | Up to Day 3 in Part A; Up to Day 30 in Part B |
| Part A & Part B:Renal clearance for AHB-171 | Up to Day 3 in Part A; Up to Day 30 in Part B |
| Part A & Part B: Immunogenicity: The number of participants develop anti-drug antibodies (ADA) against AHB-171 and the ADA antibody titer | Up to 16 weeks in Part A; Up to 48 weeks in Part B |
| Part B:Plasma Cmax of AHB-171 | Up to Day 31 |
| Part B:Plasma Tmax of AHB-171 | Up to Day 31 |
| Part B Plasma AUC of AHB-171 | Up to Day 31 |
| Part B Plasma t1/2 of AHB-171 | Up to Day 31 |
| Part B: Proportion of CHB who achieved hepatitis B surface antigen (HBsAg) clearance | Up to 48 weeks |
| Part B: HBsAg Decline in CHB Participants at each assessment time point | Up to 48 weeks |
| Part B:Proportion of participants with HBsAg < 1 IU/mL, < 10 IU/mL, and < 100 IU/mL at each assessment time point. | Up to 48 weeks |
| Part B Proportion of participants achieve seroconversion to anti-HBs (HBsAb >10 IU/L) after HBsAg loss. | Up to 48 weeks |
| Part B Proportion of participants with HBV DNA < LLOQ (10 IU/mL) | Up to 48 weeks |
| Part B Proportion of participants with HBsAg < LOD and HBV DNA < LLOQ at each assessment time point | Up to 48 weeks |
| Part B Serum levels of HBsAg, HBV DNA, HBV RNA, HBcrAg, HBsAb , HBeAb , HBeAg | Up to 48 weeks |
| Part B The level of ALT. | Up to 48 weeks |
| PartB: Proportion of participants achieving ALT normalization and time to ALT normalization among those with baseline ALT > ULN. | Up to 48 weeks |
| Part B Correlation between pharmacokinetic and pharmacodynamic parameters of AHB-171 | Up to 48 weeks |
Countries
China
Contacts
CONTACTBella Lu
Outcome results
None listed