A Phase I/IIa Trial to Evaluate the Safety, Tolerability, PK, and Preliminary Efficacy of Single and Multiple Ascending Doses of YN001 in Healthy Subjects and Multiple Ascending Doses of YN001 in Patient With Coronary Atherosclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 144
- 试验地点
- 6
- 主要终点
- Part I: The safety and tolerability of YN001 in healthy subjects.
研究概览
简要总结
This study consists of two parts. The SAD and MAD of part I are a randomized, double-blind, placebo-controlled, single and multiple ascending dose study in healthy adult subjects. The MAD expansion cohort of part I is single arm and multipal ascending dose in heallthy subjects. Part II (phase Ib/IIa) is a multicenter, randomized, controlled, open label, multiple ascending dose study in patients with coronary atherosclerosis.
详细描述
Part I (phase Ia) is consists of 2 sections. The sections 1 is designed to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of intravenously administered YN001, and to evaluate the effect of SAD of intravenously administered YN001 on the QT/QTc interval, and the immunogenicity of MAD of intravenously administered YN001 in healthy subjects. Besides, the section 2 is designed to evaluate the safety and tolerability of multiple intravenous administration of YN001 without pre-medication or with different pre-medication regimens in Chinese healthy subjects.
Part II (phase Ib/IIa) is designed to evaluate the safety, tolerability, pharmacokinetics, preliminary efficacy, immunogenicity, and the effect on cytokine changes of MAD of intravenously administered YN001 in patients with coronary atherosclerosis.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
YN001
YN001 will be administrated intravenous by single ascending dose, multiple ascending doses weekly or twice a week.
干预措施: YN001 (Drug)
Part I-Matching placebo for YN001
Matching placebo for YN001 will be administrated intravenous.
干预措施: Placebo for YN001 (Drug)
Part II-Rosuvastatin calcium tablets
Rosuvastatin calcium tablets will be given by orally.
干预措施: rosuvastatin calcium tablets (Drug)
结局指标
主要结局
Part I: The safety and tolerability of YN001 in healthy subjects.
时间窗: Up to 29 days
To evaluate the incidence of Adverse Events as Assessed by CTCAE v5.0, Clinically Significant Laboratory Abnormalities, Clinically Significant Electrocardiogram Abnormalities, Clinically Significant Vital Signs Abnormalities, Clinically Significant Physical Examination Abnormalities.
Part I: Maximum plasma concentration(Cmax) of YN001
时间窗: Up to 168 hours of post initiation of last dose
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects
Part I: Time of maximum concentration (Tmax) of YN001
时间窗: Up to 168 hours of post initiation of last dose
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
Part I: Elimination half-life (t1/2) of YN001
时间窗: Up to 168 hours of post initiation of last dose
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
Part I: Area under the plasma concentration-time curve from time 0 to the collection time point of the last measurable concentration (AUC0-t) of YN001
时间窗: Up to 168 hours of post initiation of last dose
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
Part II: The safety and tolerability of intravenously administered YN001 in patients with coronary atherosclerosis.
时间窗: Up to 29 days
To evaluate the incidence of Adverse Events as Assessed by CTCAE v5.0, Clinically Significant Laboratory Abnormalities, Clinically Significant Electrocardiogram Abnormalities, Clinically Significant Vital Signs Abnormalities, Clinically Significant Physical Examination Abnormalities, Clinically Significant Echocardiogram Abnormalities.
次要结局
- Part II: Area under the plasma concentration-time curve from time 0 to the collection time point of the last measurable concentration (AUC0-t) of YN001(Up to 96 hours of post initiation of last dose)
- Part II: Change in percent atheroma volume (PAV) of coronary plaque comparing to baseline(Up to 91 days or EOT)
- Part I: C-QTc analysis(Pre-dose and up to 48 hours post initiation of infusion)
- Part I: Pharmacodynamic evaluation(Up to 96 hours of post initiation of last dose)
- Part II: Elimination half-life (t1/2) of YN001(Up to 96 hours of post initiation of last dose)
- Part II: Maximum plasma concentration(Cmax) of YN001(Up to 96 hours of post initiation of last dose)
- Part I: Immunogenicity analysis(Up to 96 hours of post initiation of last dose)
- Part II: Time of maximum concentration (Tmax) of YN001(Up to 96 hours of post initiation of last dose)
- Part II: Change in total atheroma volume (TAV) of coronary plaque comparing to baseline(Up to 91 days or EOT)
- Part II: Change in detection rate of macrophage cluster within coronary plaque comparing to baseline(Up to 91 days or EOT)
- Part II: Change in atherosclerosis plaque located at other arteries(Up to 91 days or EOT)
- Part II: Immunogenicity analysis(Up to 91 days or EOT)
- Part II： Pharmacodynamic analysis(Up to 91 days or EOT)
- Part II: Change in minimum fibrous cap thickness (FCT) of coronary plaque comparing to baseline(Up to 91 days or EOT)
- Part II: Change in maximum IMT and plaque thickness(Up to 91 days or EOT)
- Part II: Change in coronary minimal lumen area (MLA) comparing to baseline(Up to 91 days or EOT)
- Part II: Change in maximum lipid arc and lipid core length of coronary plaque comparing to baseline(Up to 91 days or EOT)
- Part II: Cytokines analysis(Up to 91 days or EOT)