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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
144
In single ascending dose (SAD) part of study in health subjects, YN001 will be administrated one time with dosage from 10 mg to 120 mg (planned). In multiple ascending doses (MAD) part of study in health subjects, YN001 will be given twice a week from 5 mg to 40 mg up to 15 days. In MAD part of study in patients with coronary atherosclerosis, YN001 will be injected weekly or twice a week from 5mg to 40mg up to 85 days.
The injection solution to mimic the YN001
In MAD part of study in patients with coronary atherosclerosis, Rosuvastatin calcium tablets will be taken orally by 10 mg daily up to 85 days
Beijing Anzhen Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Peking University first hospital
Beijing, Beijing Municipality, China
Renmin Hospital of Wuhan University
Wuhan, Hubei, China
Zhongnan Hospital of Wuhan University
Wuhan, Hubei, China
Part I: The safety and tolerability of YN001 in healthy subjects.
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.
Time frame: Up to 29 days
Part I: Maximum plasma concentration(Cmax) of YN001
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects
Time frame: Up to 168 hours of post initiation of last dose
Part I: Time of maximum concentration (Tmax) of YN001
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
Time frame: Up to 168 hours of post initiation of last dose
Part I: Elimination half-life (t1/2) of YN001
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
Time frame: Up to 168 hours of post initiation of last dose
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
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
Time frame: Up to 168 hours of post initiation of last dose
Part II: The safety and tolerability of intravenously administered YN001 in patients with coronary atherosclerosis.
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.
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First Hospital of Jilin University
Changchun, Jilin, China
Renji Hospital Shanghai Jiaotong Unv. school of Medicine
Shanghai, Shanghai Municipality, China
Time frame: Up to 29 days
Part I: C-QTc analysis
To evaluate the effect of SAD of YN001 on QT/QTc interval prolongation and relationship between YN001 exposure and QT/QTc Interval changes in Chinese healthy subjects.
Time frame: Pre-dose and up to 48 hours post initiation of infusion
Part I: Immunogenicity analysis
To evaluate the immunogenicity of MAD of intravenously administered YN001 in Chinese healthy subjects.
Time frame: Up to 96 hours of post initiation of last dose
Part I: Pharmacodynamic evaluation
To evaluate the change LDL-C, HDL-C,TC and TG from baseline to EOT
Time frame: Up to 96 hours of post initiation of last dose
Part II: Maximum plasma concentration(Cmax) of YN001
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Time frame: Up to 96 hours of post initiation of last dose
Part II: Time of maximum concentration (Tmax) of YN001
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Time frame: Up to 96 hours of post initiation of last dose
Part II: Elimination half-life (t1/2) of YN001
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Time frame: Up to 96 hours of post initiation of last dose
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
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Time frame: Up to 96 hours of post initiation of last dose
Part II: Change in percent atheroma volume (PAV) of coronary plaque comparing to baseline
PAV will be determined by intravascular ultrasound (IVUS)
Time frame: Up to 91 days or EOT
Part II: Change in total atheroma volume (TAV) of coronary plaque comparing to baseline
TAV will be determined by intravascular ultrasound (IVUS)
Time frame: Up to 91 days or EOT
Part II: Change in coronary minimal lumen area (MLA) comparing to baseline
MLA will be determined by intravascular ultrasound (IVUS)
Time frame: Up to 91 days or EOT
Part II: Change in maximum lipid arc and lipid core length of coronary plaque comparing to baseline
lipid arc and lipid core length will be determined by optical coherence tomography (OCT)
Time frame: Up to 91 days or EOT
Part II: Change in minimum fibrous cap thickness (FCT) of coronary plaque comparing to baseline
FCT will be determined by optical coherence tomography (OCT)
Time frame: Up to 91 days or EOT
Part II: Change in detection rate of macrophage cluster within coronary plaque comparing to baseline
detection rate of macrophage cluster will be determined by optical coherence tomography (OCT)
Time frame: Up to 91 days or EOT
Part II: Change in maximum IMT and plaque thickness
IMT will be determined by carotid ultrasound scans
Time frame: Up to 91 days or EOT
Part II: Change in atherosclerosis plaque located at other arteries
Other arteries plaque will be determined by CTA or MRA
Time frame: Up to 91 days or EOT
Part II: Immunogenicity analysis
To evaluate the immunogenicity of MAD of intravenously administered YN001 in Chinese patients with coronary atherosclerosis.
Time frame: Up to 91 days or EOT
Part II: Cytokines analysis
To evaluate the effect of MAD of intravenously administered YN001 on Cytokines levels in Chinese patients with coronary atherosclerosis.
Time frame: Up to 91 days or EOT
Part II: Pharmacodynamic analysis
Change in LDL-C,HDL-C,TC and TG levels form baseline to EOT
Time frame: Up to 91 days or EOT