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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Part A:Plasma Cmax of AHB-171
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
AHB-171 and placebo in CHB (Part B: MAD)
Drug: AHB-171 Injection Drug: Placebo Drug: Nucleos(t)ide Analogue (NA) Background treatment
干预措施: AHB-171 Injection (Drug)
AHB-171 and placebo in HP(Part A: SAD)
Drug: AHB-171Injection Drug: Placebo
干预措施: Placebo (Drug)
AHB-171 and placebo in CHB (Part B: MAD)
Drug: AHB-171 Injection Drug: Placebo Drug: Nucleos(t)ide Analogue (NA) Background treatment
干预措施: Placebo (Drug)
AHB-171 and placebo in CHB (Part B: MAD)
Drug: AHB-171 Injection Drug: Placebo Drug: Nucleos(t)ide Analogue (NA) Background treatment
干预措施: Nucleos(t)ide Analogue (NA) (Drug)
AHB-171 and placebo in HP(Part A: SAD)
Drug: AHB-171Injection Drug: Placebo
干预措施: AHB-171 Injection (Drug)
结局指标
主要结局
Part A:Plasma Cmax of AHB-171
时间窗: Up to Day 8
Part A:Plasma Tmax of AHB-171
时间窗: Up to Day 8
Part A Plasma AUC of AHB-171
时间窗: Up to Day 8
Part A & Part B Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs); proportion of participants with clinically significant abnormal laboratory tests, electrocardiograms (ECGs), physical examinations, and
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Part A Plasma t1/2 of AHB-171
时间窗: Up to Day 8
Proportion of participants with other vital signs
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Change from baseline in laboratory tests
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Change from baseline in physical examinations
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Change from baseline in vital signs
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Change from baseline in electrocardiograms (ECGs)
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Proportion of participants with clinically significant abnormalities in laboratory tests
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Proportion of participants with clinically significant abnormalities in electrocardiograms (ECGs)
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
Proportion of participants with physical examinations
时间窗: PartA:Up to 16 weeks, PartB: Up to 48 weeks
次要结局
- Part B Plasma t1/2 of AHB-171(Up to Day 31)
- 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: 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)