- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06048588
YN001 in Healthy Subjects and Patients With Coronary Atherosclerosis
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jamie Zhang, Master
- Phone Number: 861082599080
- Email: zhangjingmei@innovmed.co
Study Locations
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Beijing
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Beijing, Beijing, China, 100034
- Recruiting
- Peking University First Hospital
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Contact:
- Jianping Li, PhD
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Principal Investigator:
- Jianping Li, Ph.D
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Principal Investigator:
- Xia Zhao, Master
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Beijing, Beijing, China, 10000
- Recruiting
- Beijing Anzhen Hospital, Capital Medical University
-
Contact:
- Yang Lin, Ph.D
- Phone Number: 861064456014
- Email: linyang@anzhengcp.com
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Principal Investigator:
- Yang Lin, Ph.D
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Principal Investigator:
- Dongmei Shi, Master
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Hubei
-
Wuhan, Hubei, China
- Recruiting
- Zhongnan Hospital of Wuhan University
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Contact:
- Zhibing Lu, Ph.D
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Wuhan, Hubei, China
- Recruiting
- Renmin Hospital of Wuhan University
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Contact:
- Hong Jiang, Ph.D
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Jilin
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Changchun, Jilin, China, 130000
- Recruiting
- First Hospital of Jilin University
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Contact:
- Yanhua Ding, Ph.D
- Phone Number: 86043188782168
- Email: dingyanhua2003@126.com
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Principal Investigator:
- Qian Tong, Ph.D
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Principal Investigator:
- Yanhua Ding, Ph.D
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Shanghai
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Shanghai, Shanghai, China
- Recruiting
- Renji Hospital Shanghai Jiaotong Unv. school of Medicine
-
Contact:
- Jun Pu, Ph.D
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Part I (Phase Ia)-Inclusion criteria:
- Fully understand the purposes, features, and methods of the study and the possible adverse reactions, voluntarily participate in the study as a subject, and sign the ICF before performing any assessment.
- Chinese healthy male or female subjects between 18 and 55 years.
- A Body Mass Index (BMI) of 18-28 kg/m2 (inclusive), with a body weight of at least 50 kg for males and 45 kg for females.
- Be in good general health at discretion of the investigator based on the results (be normal or abnormal without clinical significance) of medical history, physical examination, vital signs,12-lead ECG, laboratory tests (Hematology; Blood chemistry; Urinalysis, Coagulation and CRP) and viral serology.
- Female subjects must be non-pregnant and non-lactating, and women of childbearing potential (including the male subject's female companion) must agree to use effective method of contraception from the screening period to 3 months after receiving their last dose of the investigational drug.
- Willing and able to comply with the requirements of protocol.
Part I (Phase Ia)-Exclusion criteria:
- Prior treatment with other investigational drug(s) within 3 months or 5 half-lives, whichever is longer, prior to the first dosing.
- Prior treatment with any prescription drugs, herbal supplements, over the counter (OTC) medication, dietary supplements (vitamins included), or any type of vaccination within 2 weeks prior to the first dosing.
- Presenting with history of severe food allergy (e.g., anaphylactic reaction). Mild (e.g., non-anaphylactic, hypersensitivity) food allergies such as lactose intolerance/ glucose intolerance are permitted.
- Allergy to multiple kinds of drugs or presenting with history of allergic reactions to any components of the study drug.
- Known any clinically abnormal diseases or factors, including but not limited to neurological, cardiovascular, hematological, hepatic, renal, gastrointestinal, respiratory, metabolic, endocrine, immunological, skeletal system diseases, or other reasons that, in the opinion of the investigator, makes the subject inappropriate for inclusion in this study.
- Presenting with history of myopathy/ myalgia, or susceptible to myopathy/ rhabdomyolysis.
- Presence of hypothyroidism.
- Presenting and/or relapse history (within the last 3 years) of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated, or not treated) or cardiac dysfunction or myocardial infarction.
- Known inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding within 6 months prior to the first dosing.
- Presenting with history of pancreatic injury or pancreatitis within 6 months prior to the first dosing.
- Presence of symptoms of urinary obstruction or difficulty in voiding.
- Presenting and/ or relapse history (within the last 3 years) of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).
- Evidence of major diseases that not recovered within 2 weeks prior to the first dosing, or major surgery is expected during the study.
- Presenting with history of impaired renal function defined by clinically significantly abnormal creatinine or BUN and/ or urea values, or abnormal urinary constituents (e.g., albuminuria).
- Presence of liver disease or liver injury, defined by abnormal liver function tests.
- Fasting triglyceride > 3.4 mmol/L.
- Presenting with history of clinically significant ECG abnormalities, or any of the following abnormalities at screening or baseline. QTcF>470 msec for male, QTcF>480 msec for female.
- Hemoglobin levels are below 120 g/L for males and 110 g/L for females at screening.
- Donation or blood loss is more than 400 mL within 3 months prior to screening.
- Use more than 10 cigarettes per day or habitual use of nicotine-containing products within 3 months prior to screening.
- Presenting with history of drug abuse within 12 months prior to screening, or use of any drugs within 3 months prior to screening, or a positive result of drug abuse screen at screening.
- Consumption of more than 14 standard drinks of alcohol per week within 3 months prior to screening, or consumption of alcohol-containing products 48 hours prior to the first dosing or having positive alcohol breath test at baseline.
- Positive for HBsAg, HCV, HIV, TP-Ab.
- Presence of any other diseases or conditions that, in the opinion of the investigator, would make it unsuitable for the subject to participate in this study.
Part II (Phase Ib/IIa)-Inclusion criteria:
- Fully understand the purposes, features, and methods of the study and the possible adverse reactions, voluntarily participate in the study as a subject, and sign the ICF before performing any assessment.
- Chinese male or female subjects between 18 and 75 years.
- Patients diagnosed with confirmed coronary atherosclerosis and 25-75% stenosis determined by coronary angiography.
- Suspicion of vulnerable plaque based on clinical practice and determined by OCT examination.
- Measurable targeted segment by estimation must be at least 40 mm in length.
- Female subjects must be non-pregnant and non-lactating, and women of childbearing potential (including the male subject's female companion) must agree to use effective method of contraception from the screening period to 3 months after receiving their last dose of the investigational drug.
- Willing and able to comply with the requirements of protocol.
Part II (Phase Ib/IIa)-Exclusion criteria:
- Prior treatment with other investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to the first dosing.
- Any type of vaccination within 4 weeks prior to the first dosing.
- Presence of moderate or heavily calcification lesion in target segment determined by coronary angiography.
- Known familial hypercholesterolemia.
- Relapse and highly symptomatic arrhythmia uncontrolled by drugs within the past 3 months, such as ventricular tachycardia, atrial fibrillation with rapid ventricular rate and paroxysmal supraventricular tachycardia.
- Presenting with history of any type of stroke (cerebral lacunar infarction excluded).
- Presenting with history of myopathy/ myalgia, or susceptible to myopathy/ rhabdomyolysis.
- Known inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding within 6 months prior to the first dosing.
- Presenting with history of pancreatic injury or pancreatitis within 6 months prior to the first dosing.
- Evidence of major diseases that not recovered within 2 weeks prior to the first dosing, or major surgery is expected during the study.
- Any surgical operation is planned during the study.
- Presenting with history of malignancy.
- Presence of any type of autoimmune disease.
- Allergy to multiple food or drugs or presenting with history of allergic reactions to any components of the study drug.
- Prior treatment with CABG, PCI, heart transplantation, SAVR/TAVR, etc., or CABG, PCI, heart transplantation, SAVR/TAVR, etc., is planned during the study.
- Life expectancy is less than 1 year.
- Left ventricular ejection fraction (LVEF) <40%.
- Left main coronary artery disease, defined as left main coronary artery stenosis≥50% by angiographic estimation.
- Uncontrolled hypertension.
- Active liver disease or hepatic dysfunction defined by any of ALT, AST, or serum bilirubin exceeding 1.5ULN.
- Presence of renal insufficiency (eGFR < 30 mL/min/1.73m2).
- Presence of hypothyroidism.
- Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus.
- Positive for HBsAg, HCV, HIV, TP-Ab.
- Presence of any other diseases or conditions that, in the opinion of the investigator, would make it unsuitable for the subject to participate in this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: YN001
YN001 will be administrated intravenous by single ascending dose, multiple ascending doses weekly or twice a week.
|
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.
|
Placebo Comparator: Part I-Matching placebo for YN001
Matching placebo for YN001 will be administrated intravenous.
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The injection solution to mimic the YN001
Other Names:
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Active Comparator: Part II-Rosuvastatin calcium tablets
Rosuvastatin calcium tablets will be given by orally.
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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
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part I: Maximum plasma concentration(Cmax) of YN001
Time Frame: Up to 168 hours of post initiation of last dose
|
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects
|
Up to 168 hours of post initiation of last dose
|
Part I: Time of maximum concentration (Tmax) of YN001
Time Frame: Up to 168 hours of post initiation of last dose
|
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
|
Up to 168 hours of post initiation of last dose
|
Part I: Elimination half-life (t1/2) of YN001
Time Frame: Up to 168 hours of post initiation of last dose
|
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
|
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
Time Frame: Up to 168 hours of post initiation of last dose
|
To evaluate the pharmacokinetics (PK) characteristics of of intravenously administered YN001 in healthy subjects.
|
Up to 168 hours of post initiation of last dose
|
Part I: The safety and tolerability of YN001 in healthy subjects.
Time Frame: 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.
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Up to 29 days
|
Part II: The safety and tolerability of intravenously administered YN001 in patients with coronary atherosclerosis.
Time Frame: 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.
|
Up to 29 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part I: C-QTc analysis
Time Frame: 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.
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Pre-dose and up to 48 hours post initiation of infusion
|
Part I: Immunogenicity analysis
Time Frame: Up to 96 hours of post initiation of last dose
|
To evaluate the immunogenicity of MAD of intravenously administered YN001 in Chinese healthy subjects.
|
Up to 96 hours of post initiation of last dose
|
Part II: Maximum plasma concentration(Cmax) of YN001
Time Frame: 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.
|
Up to 96 hours of post initiation of last dose
|
Part II: Time of maximum concentration (Tmax) of YN001
Time Frame: 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.
|
Up to 96 hours of post initiation of last dose
|
Part II: Elimination half-life (t1/2) of YN001
Time Frame: 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.
|
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
Time Frame: 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.
|
Up to 96 hours of post initiation of last dose
|
Part I: Pharmacodynamic evaluation
Time Frame: 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
|
Up to 96 hours of post initiation of last dose
|
Part II: Change in percent atheroma volume (PAV) of coronary plaque comparing to baseline
Time Frame: Up to 91 days or EOT
|
PAV will be determined by intravascular ultrasound (IVUS)
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Up to 91 days or EOT
|
Part II: Change in total atheroma volume (TAV) of coronary plaque comparing to baseline
Time Frame: Up to 91 days or EOT
|
TAV will be determined by intravascular ultrasound (IVUS)
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Up to 91 days or EOT
|
Part II: Change in coronary minimal lumen area (MLA) comparing to baseline
Time Frame: Up to 91 days or EOT
|
MLA will be determined by intravascular ultrasound (IVUS)
|
Up to 91 days or EOT
|
Part II: Change in maximum lipid arc and lipid core length of coronary plaque comparing to baseline
Time Frame: Up to 91 days or EOT
|
lipid arc and lipid core length will be determined by optical coherence tomography (OCT)
|
Up to 91 days or EOT
|
Part II: Change in minimum fibrous cap thickness (FCT) of coronary plaque comparing to baseline
Time Frame: Up to 91 days or EOT
|
FCT will be determined by optical coherence tomography (OCT)
|
Up to 91 days or EOT
|
Part II: Change in detection rate of macrophage cluster within coronary plaque comparing to baseline
Time Frame: Up to 91 days or EOT
|
detection rate of macrophage cluster will be determined by optical coherence tomography (OCT)
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Up to 91 days or EOT
|
Part II: Change in maximum IMT and plaque thickness
Time Frame: Up to 91 days or EOT
|
IMT will be determined by carotid ultrasound scans
|
Up to 91 days or EOT
|
Part II: Change in atherosclerosis plaque located at other arteries
Time Frame: Up to 91 days or EOT
|
Other arteries plaque will be determined by CTA or MRA
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Up to 91 days or EOT
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Part II: Immunogenicity analysis
Time Frame: Up to 91 days or EOT
|
To evaluate the immunogenicity of MAD of intravenously administered YN001 in Chinese patients with coronary atherosclerosis.
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Up to 91 days or EOT
|
Part II: Cytokines analysis
Time Frame: 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.
|
Up to 91 days or EOT
|
Part II: Pharmacodynamic analysis
Time Frame: Up to 91 days or EOT
|
Change in LDL-C,HDL-C,TC and TG levels form baseline to EOT
|
Up to 91 days or EOT
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Teresa Chen, Master, Beijing Inno Medicine Co., Ltd.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Heart Diseases
- Vascular Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Coronary Disease
- Coronary Artery Disease
- Myocardial Ischemia
- Cardiovascular Diseases
- Atherosclerosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Calcium-Regulating Hormones and Agents
- Rosuvastatin Calcium
- Calcium
Other Study ID Numbers
- YN001-002
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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