YN001 in Healthy Subjects and Patients With Coronary Atherosclerosis
- Conditions
- Atherosclerotic Cardiovascular Disease
- Interventions
- Registration Number
- NCT06048588
- Lead Sponsor
- Beijing Inno Medicine Co., Ltd.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 130
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description YN001 YN001 YN001 will be administrated intravenous by single ascending dose, multiple ascending doses weekly or twice a week. Part I-Matching placebo for YN001 Placebo for YN001 Matching placebo for YN001 will be administrated intravenous. Part II-Rosuvastatin calcium tablets rosuvastatin calcium tablets Rosuvastatin calcium tablets will be given by orally.
- Primary Outcome Measures
Name Time Method Part I: The safety and tolerability of YN001 in healthy subjects. 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 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 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 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 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. 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.
- Secondary Outcome Measures
Name Time Method 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 To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Part II: Change in percent atheroma volume (PAV) of coronary plaque comparing to baseline Up to 91 days or EOT PAV will be determined by intravascular ultrasound (IVUS)
Part I: C-QTc analysis Pre-dose and up to 48 hours post initiation of infusion 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.
Part I: Pharmacodynamic evaluation Up to 96 hours of post initiation of last dose To evaluate the change LDL-C, HDL-C,TC and TG from baseline to EOT
Part II: Elimination half-life (t1/2) of YN001 Up to 96 hours of post initiation of last dose To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Part I: Immunogenicity analysis Up to 96 hours of post initiation of last dose To evaluate the immunogenicity of MAD of intravenously administered YN001 in Chinese healthy subjects.
Part II: Maximum plasma concentration(Cmax) of YN001 Up to 96 hours of post initiation of last dose To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Part II: Time of maximum concentration (Tmax) of YN001 Up to 96 hours of post initiation of last dose To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in patients with coronary atherosclerosis.
Part II: Change in total atheroma volume (TAV) of coronary plaque comparing to baseline Up to 91 days or EOT TAV will be determined by intravascular ultrasound (IVUS)
Part II: Change in detection rate of macrophage cluster within coronary plaque comparing to baseline Up to 91 days or EOT detection rate of macrophage cluster will be determined by optical coherence tomography (OCT)
Part II: Change in atherosclerosis plaque located at other arteries Up to 91 days or EOT Other arteries plaque will be determined by CTA or MRA
Part II: Immunogenicity analysis Up to 91 days or EOT To evaluate the immunogenicity of MAD of intravenously administered YN001 in Chinese patients with coronary atherosclerosis.
Part II： Pharmacodynamic analysis Up to 91 days or EOT Change in LDL-C,HDL-C,TC and TG levels form baseline to EOT
Part II: Change in minimum fibrous cap thickness (FCT) of coronary plaque comparing to baseline Up to 91 days or EOT FCT will be determined by optical coherence tomography (OCT)
Part II: Change in maximum IMT and plaque thickness Up to 91 days or EOT IMT will be determined by carotid ultrasound scans
Part II: Change in coronary minimal lumen area (MLA) comparing to baseline Up to 91 days or EOT MLA will be determined by intravascular ultrasound (IVUS)
Part II: Change in maximum lipid arc and lipid core length of coronary plaque comparing to baseline Up to 91 days or EOT lipid arc and lipid core length will be determined by optical coherence tomography (OCT)
Part II: Cytokines analysis Up to 91 days or EOT To evaluate the effect of MAD of intravenously administered YN001 on Cytokines levels in Chinese patients with coronary atherosclerosis.
Trial Locations
- Locations (6)
Beijing Anzhen Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Peking University first hospital
🇨🇳Beijing, Beijing, China
Renji Hospital Shanghai Jiaotong Unv. school of Medicine
🇨🇳Shanghai, Shanghai, China
First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China