A Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, Dose-escalation Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profiles of AK0406 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
This study is a phase I, single-center, randomized, double-blind, placebo-controlled study of AK0406 as a first-in-human (FIH) trial to evaluate the safety, tolerability and pharmacokinetics (PK) of AK0406 in healthy adult participants.
详细描述
This study consists of four cohorts: Cohort A: 150 milligram (mg) subcutaneous injection (s.c.) Cohort B: 300 mg s.c. Cohort C: 600 mg s.c. Cohort D: 900 mg s.c. Each cohort will enroll 8 healthy adult participants (AK0406: placebo = 3: 1), including both females and males. Dose escalation will follow a sequential order, beginning with the lowest dose 150 mg and proceeding to 300 mg, 600 mg, and finally 900 mg. A sentinel-dosing strategy will be implemented. For the first cohort (Cohort A) and the last cohort (Cohort D): the first two participants (1 AK0406, 1 placebo) will be dosed and observed for at least 7 days. The first two participants (1 AK0406, 1 placebo) in Cohort B and Cohort C will be dosed and observed for over 48 hours. After both the investigator and sponsor agree with the acceptable safety and tolerability profile, the remaining 6 participants (5 AK0406, 1 placebo) in that cohort will be dosed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Male or female participants aged 18 to 65 years (inclusive) at the time of formed consent.
- •At screening, male participants must weigh ≥50 kilogram (kg), and female participants must weigh ≥45 kg, with a body mass index between 18.0 and 32.0 kilograms per square meter (kg/m²) (inclusive).
- •Participants must be in good general health as determined by the investigator, with no clinically significant abnormalities in vital signs, 12-lead electrocardiogram (ECG), or laboratory tests.
- •Woman of childbearing potential (WOCBP) and male participants whose female sexual partner is WOCBP must agree to use highly effective contraception from the day of study drug administration until 6 months after dosing and must agree to avoid sperm or oocyte donation and not plan to conceive during this period.
- •Participants must voluntarily agree to participate, be able to communicate effectively with the investigator, understand and comply with study requirements, and provide written informed consent.
排除标准
- •Presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic (e.g., bleeding disorders), gastrointestinal, endocrine, immune, dermatologic, neurologic, or psychiatric disease, or any other condition that, in the opinion of the investigator, may compromise participant safety, interfere with study results, or prevent completion of the study.
- •Active malignancy or history of malignancy (except adequately treated basal cell carcinoma with no evidence of recurrence).
- •History of congenital or acquired immunodeficiency.
- •Acute illness (e.g., fever, infectious disease, diarrhea) within 7 days prior to first dosing.
- •Major surgery within 3 months before screening or planned major surgery within 6 months after study drug administration.
- •Known hypersensitivity to neuraminidase inhibitors (e.g., oseltamivir, zanamivir, peramivir), or to AK0406 active ingredient or any excipients.
- •Anaphylaxis or severe hypersensitivity (e.g., hypotension, dyspnea, severe angioedema).
- •Diagnostic Assessments
- •Positive for Human immunodeficiency virus (HIV) antibody, Hepatitis C virus (HCV) antibody, Hepatitis B surface antigen (HBsAg), or Treponema pallidum antibody.
- •Systolic blood pressure >140 millimeters of mercury (mmHg) or ≤90 mmHg, diastolic blood pressure ≥90 mmHg or ≤50 mmHg, or pulse ≤45 or ≥110 beats per minute (bpm) while awake and at rest.
- •The Corrected QT interval by Fredericia (QTcF) prolongation (up to 450 ms in males / 470 milliseconds (ms) in females) at screening. [QTcF = QT/(RR^0.33)] (RR = 60/heart rate)
研究组 & 干预措施
Placebo
干预措施: 0.9% Sodium Chloride Injection as Placebo (Drug)
Cohort A: AK0406 150 mg
干预措施: AK0406 150 mg (Drug)
Cohort B：AK0406 300 mg
干预措施: AK0406 300 mg (Drug)
Cohort C：AK0406 600 mg
干预措施: AK0406 600 mg (Drug)
Cohort D：AK0406 900 mg
干预措施: AK0406 900 mg (Drug)
结局指标
主要结局
Adverse events
时间窗: Up to Day 181
Capture the incidence and severity of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 6.0 throughout the study period.
次要结局
- Maximum concentration(Pre-dose, Day 1, Day 3, Day 5, Day 7, Day 15, Day 22, Day 31, Day 61, Day 91, Day 121, Day 151, Day 181)
- Time to maximum concentration(Pre-dose, Day 1, Day 3, Day 5, Day 7, Day 15, Day 22, Day 31, Day 61, Day 91, Day 121, Day 151, Day 181)
- Area under the drug concentration-time curve from time 0 to the last measurable concentration(Pre-dose, Day 1, Day 3, Day 5, Day 7, Day 15, Day 22, Day 31, Day 61, Day 91, Day 121, Day 151, Day 181)
- Area under the drug concentration-time curve from time 0 to extrapolated to infinite time(Pre-dose, Day 1, Day 3, Day 5, Day 7, Day 15, Day 22, Day 31, Day 61, Day 91, Day 121, Day 151, Day 181)
- Terminal half-life(Pre-dose, Day 1, Day 3, Day 5, Day 7, Day 15, Day 22, Day 31, Day 61, Day 91, Day 121, Day 151, Day 181)
- Apparent clearance(Pre-dose, Day 1, Day 3, Day 5, Day 7, Day 15, Day 22, Day 31, Day 61, Day 91, Day 121, Day 151, Day 181)
- Apparent volume of distribution(Pre-dose, Day 1, Day 3, Day 5, Day 7, Day 15, Day 22, Day 31, Day 61, Day 91, Day 121, Day 151, Day 181)
- Incidence and titer of anti-drug antibodies(Baseline, Day 15, Day 31, Day 91, Day 181)