A Phase I Clinical Study of AHB - 171 in Healthy Participants(HP) and Chronic Hepatitis B (CHB) Participants

Official title

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AHB - 171 Injection in Healthy Participants (HP) and Chronic Hepatitis B(CHB) Participants

Overview

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

• Drug AHB-171 Injection
  AHB-171 Injection is adminstrated via subcutaneous injection
• Drug Placebo
  Placebo is admistrated via subcutaneous injection
• Drug Nucleos(t)ide Analogue (NA)
  Oral administration

Primary outcome measures

• Part A & Part B Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time frame: PartA:Up to 16 weeks, PartB: Up to 48 weeks]
• Severity of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time frame: PartA:Up to 16 weeks, PartB: Up to 48 weeks]
• Change from baseline in laboratory tests [Time frame: PartA:Up to 16 weeks, PartB: Up to 48 weeks]
• Change from baseline in physical examinations [Time frame: PartA:Up to 16 weeks, PartB: Up to 48 weeks]
• Change from baseline in vital signs [Time frame: PartA:Up to 16 weeks, PartB: Up to 48 weeks]
• Change from baseline in electrocardiograms (ECGs) [Time frame: PartA:Up to 16 weeks, PartB: Up to 48 weeks]
• Part A:Plasma Cmax of AHB-171 [Time frame: Up to Day 8]
• Part A:Plasma Tmax of AHB-171 [Time frame: Up to Day 8]
• Part A Plasma AUC of AHB-171 [Time frame: Up to Day 8]
• Part A Plasma t1/2 of AHB-171 [Time frame: Up to Day 8]

Secondary outcome measures (12)

• Part A & Part B:Fraction excreted in urine in percentage for AHB-171 [Time frame: 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 [Time frame: Up to Day 3 in Part A; Up to Day 30 in Part B]
• Part A & Part B:Renal clearance for AHB-171 [Time frame: 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 [Time frame: Up to 16 weeks in Part A; Up to 48 weeks in Part B]
• Part B:Plasma Cmax of AHB-171 [Time frame: Up to Day 31]
• Part B:Plasma Tmax of AHB-171 [Time frame: Up to Day 31]
• Part B Plasma AUC of AHB-171 [Time frame: Up to Day 31]
• Part B Plasma t1/2 of AHB-171 [Time frame: Up to Day 31]
• Part B: Proportion of CHB who achieved hepatitis B surface antigen (HBsAg) clearance [Time frame: Up to 48 weeks]
• Part B: HBsAg Decline in CHB Participants at each assessment time point [Time frame: 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. [Time frame: Up to 48 weeks]
• Part B Proportion of participants achieve seroconversion to anti-HBs (HBsAb >10 IU/L) after HBsAg loss. [Time frame: Up to 48 weeks]

Eligibility criteria

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.

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

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• AusperBio Investigational Site — Ch’ang-ch’un
• AusperBio Investigational Site — Hangzhou

Identifiers

NCT: NCT07511218 · AB-17-8002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗