A Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Dose-Escalation, and Expansion Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of AK0610 in Healthy Chinese Adults.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 136
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
The study consists of two parts: dose escalation and expansion. It includes five cohorts in the dose-escalation phase and two expansion cohorts based on pharmacokinetic data.
详细描述
This study is a Phase I clinical trial that is randomized, double-blind, placebo-controlled, and involves single-dose administration, dose-escalation, and an expansion phase. It evaluates the safety, tolerability, and pharmacokinetic profile of AK0610 in healthy Chinese adults.
The study consists of two parts. The dose-escalation phase includes five cohorts (100 mg i.m.; 300 mg i.m.; 300 mg i.v.; 1000 mg i.v.; 3000 mg i.v.), each consisting of 8 individuals (AK0610: Placebo = 3:1), who are administered doses in sequential increments.
Based on pharmacokinetic data, the dose-escalation phase will be expanded to include two additional dose cohorts (300 mg i.m.; 600 mg i.m.) of 48 individuals each (AK0610: Placebo = 3:1).
Each participant will undergo a Screening Period from Day -29 to Day -1. They will receive one dose on Day 1, an Inpatient Observation Period from Day -1 to Day 8, and a Blinded Follow-Up Period from Day 9 to Day 181. Subjects in the AK0610 group will also enter an open-label period from Day 182 to Day 361.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants aged 18 - 50 (both males and females)
- •Males weighing ≥50 kg, females weighing ≥45 kg, and BMI 18-28 kg/m
- •Assessed by the investigator to be in good health with no clinically significant abnormalities.
- •Use of highly effective contraception within 1 year of administration.
- •Voluntary participation in clinical research and signing of written informed consent.
排除标准
- •Clinically significant cardiovascular, respiratory, hepatic, renal, hematologic (e.g., bleeding disorders), gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric system disorders, or any other condition that, in the opinion of the Investigator, may jeopardize subject safety or validity of the study results, or that may result in the inability of the subject to complete the study in accordance with the protocol.
- •Active malignancy and/or a history of malignancy (except for basal cell carcinoma of the skin that has been treated without evidence of recurrence)
- •History of congenital or acquired immunodeficiency.
- •Acute illness, such as fever, infectious disease, diarrhea, etc., occurring within 1 week prior to the subject's first dose.
- •Major surgery within 3 months prior to screening or major surgery planned within 1 year of study drug administration.
- •Hypersensitivity to the active ingredient of AK0610 or any excipients.
- •Previous history of allergy to biologics or history of severe allergic reaction (e.g. hypotension, dyspnea, severe angioedema) to any drug.
- •Human immunodeficiency virus (HIV) antibody positive; hepatitis C virus (HCV) antibody positive or hepatitis B surface antigen (HBsAg) positive; syphilis spirochete antibody positive.
- •Systolic blood pressure ≥140 mmHg or <90 mmHg or diastolic blood pressure ≥90 mmHg or <60 mmHg, and pulse <55 or >100 beats/min.
- •ECG suggestive of prolonged QTcF (≥450 ms in both women and men). [QTcF= QT/(RR^0.33)]
- •Use of any prescription, over-the-counter, herbal, proprietary, or health care product (other than birth control pills) within 14 days prior to study drug administration.
- •Have received treatment with immune globulin or other blood products within 6 months prior to study drug administration
- •Have received treatment with monoclonal antibodies or other biological products within 6 months prior to administration of study drug.
- •Have received a live attenuated vaccination within 1 month prior to study drug administration, has received another vaccination within 14 days, or is scheduled to receive a vaccination within 1 year of study drug administration.
- •Received any other investigational drug therapy within 3 months (or 5 half-lives, whichever is longer) prior to study drug administration, or plans to participate in another study within 1 year of study drug administration.
- •Participating or have participated in another interventional clinical study of a monoclonal antibody or vaccine against RSV.
研究组 & 干预措施
Escalation Phase Cohort 1: AK0610 Injection 100 mg or placebo 1 ml
AK0610 100 mg or Placebo 1 ml，Intramuscular injection，once on Day 1.
干预措施: AK0610 Injection solution (Drug)
Escalation Phase Cohort 1: AK0610 Injection 100 mg or placebo 1 ml
AK0610 100 mg or Placebo 1 ml，Intramuscular injection，once on Day 1.
干预措施: Placebo (Drug)
Escalation Phase Cohort 2: AK0610 Injection 300 mg or Placebo 3 ml
AK0610 300 mg or Placebo 3 ml，Intramuscular injection，once on Day 1.
干预措施: AK0610 Injection solution (Drug)
Escalation Phase Cohort 2: AK0610 Injection 300 mg or Placebo 3 ml
AK0610 300 mg or Placebo 3 ml，Intramuscular injection，once on Day 1.
干预措施: Placebo (Drug)
Escalation Phase Cohort 3: AK0610 Injection 300 mg or Placebo 3 ml
AK0610 300 mg or Placebo 3 ml，Intravenous injection，once on Day 1.
干预措施: AK0610 Injection solution (Drug)
Escalation Phase Cohort 3: AK0610 Injection 300 mg or Placebo 3 ml
AK0610 300 mg or Placebo 3 ml，Intravenous injection，once on Day 1.
干预措施: Placebo (Drug)
Escalation Phase Cohort 4: AK0610 Injection 1000 mg or Placebo 10 ml
AK0610 1000 mg or Placebo 10 ml，Intravenous injection，once on Day 1.
干预措施: AK0610 Injection solution (Drug)
Escalation Phase Cohort 4: AK0610 Injection 1000 mg or Placebo 10 ml
AK0610 1000 mg or Placebo 10 ml，Intravenous injection，once on Day 1.
干预措施: Placebo (Drug)
Escalation Phase Cohort 5: AK0610 Injection 3000 mg or Placebo 30 ml
AK0610 3000 mg or Placebo 30 ml，Intravenous injection，once on Day 1.
干预措施: AK0610 Injection solution (Drug)
Escalation Phase Cohort 5: AK0610 Injection 3000 mg or Placebo 30 ml
AK0610 3000 mg or Placebo 30 ml，Intravenous injection，once on Day 1.
干预措施: Placebo (Drug)
Expansion Phase Cohort 6: AK0610 Injection 300 mg or Placebo 3 ml
AK0610 300 mg or Placebo 3 ml，Intramuscular injection，once on Day 1.
干预措施: AK0610 Injection solution (Drug)
Expansion Phase Cohort 6: AK0610 Injection 300 mg or Placebo 3 ml
AK0610 300 mg or Placebo 3 ml，Intramuscular injection，once on Day 1.
干预措施: Placebo (Drug)
Expansion Phase Cohort 7: AK0610 Injection 600 mg or Placebo 6 ml
AK0610 600mg or Placebo 6ml，Intramuscular injection，once on Day 1.
干预措施: AK0610 Injection solution (Drug)
Expansion Phase Cohort 7: AK0610 Injection 600 mg or Placebo 6 ml
AK0610 600mg or Placebo 6ml，Intramuscular injection，once on Day 1.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: Up to 361 days
Capture the incidence and severity of adverse events using CTCAE v5.0, documenting all treatment-emergent adverse events (TEAEs) throughout the study period.
次要结局
- Maximum Observed Serum Concentration (Cmax) of AK0610(Up to 361 days)
- Time to Reach Maximum Observed Serum Concentration (Tmax) of AK0610(Up to 361 days)
- Area Under the serum concentration-time curve from time 0 to the last measurable concentration (AUC₀-t) of AK0610(Up to 361 days)
- Area Under the serum concentration-time curve from time 0 to extrapolated to infinite time (AUC (0-infinity) ) of AK0610(Up to 361 days)
- Terminal Elimination Half Life (t1/2) of AK0610(Up to 361 days)
- Extravascular Clearance (CL/F (intramuscular administration)) of AK0610(Up to 361 days)
- Apparent Volume of Distribution (Vd/F (intramuscular administration)) of AK0610(Up to 361 days)
- CL(IV administration) of AK0610(Up to 361 days)
- Vd (IV administration) of AK0610(Up to 361 days)
- To assess the changes in serum RSV-neutralizing activity after a single intramuscular or intravenous injection of AK0610 in healthy Chinese subjects(Up to 361 days)
- To assess the immunogenicity of a single intramuscular or intravenous injection of AK0610 in healthy Chinese subjects.(Up to 361 days)