A Phase Ⅱa Clinical Study to Evaluate the Efficacy and Safety of YN001 in Patients With Coronary Atherosclerosis in Australia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 10
- 主要终点
- Changes in coronary plaque characteristics (volume and composition)
研究概览
简要总结
This study is to evaluate the efficacy and safety of intravenously administered YN001 in patients with coronary atherosclerosis in Australia. This study will be conducted in eligible participants with a diagnosis of coronary atherosclerosis, and at least 1 coronary artery is blocked determined by coronary computed tomography angiography (CCTA)
详细描述
This is a multicenter, randomized, open label, parallel-group, proof of concept study. It is designed to determine if the study drug, called YN001, administered in addition to evolocumab can effectively reduce the total amount of plaque formed in the coronary artery as measured by CCTA from baseline to week 13.
A total of 24 patients with coronary atherosclerosis are expected to be enrolled and will be randomly assigned in a 1:1 ratio to 1 of 2 YN001 treatment arms (12 patients per arm) with 2 different dose levels for 12 weeks.
The study will be comprised of a maximum 41-day screening period (Day -42-Day -2), a baseline period (Day-1), a treatment and observation period (W1D1- W13D7), and a safety follow-up period (14 days post last dose).
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
- Single (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
- 否
入选标准
- •Fully understand the purposes, features, and methods of the study, and sign the ICF before performing any assessment.
- •Male or female Australia patients between 18 and 75 years.
- •Patients diagnosed with coronary atherosclerosis, and at least 1 vessel with diameter stenosis determined by coronary computed tomography angiography (CTA).
- •Female patients must be non-pregnant and non-lactating, and females of childbearing potential (including a female partner of a male patient) must agree to use 1 effective contraception method from the screening period to 3 months after receiving their last dose of the study drug. In addition, male patients must be willing to refrain from sperm donation during this time.
- •Willing and able to comply with the requirements of protocol to the best of the patient's and investigator's knowledge.
排除标准
- •Prior treatment with other investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to randomization.
- •Previously received YN
- •Any type of vaccination within 4 weeks prior to randomization.
- •Contraindication for coronary CTA (e.g., known history of anaphylactic contrast reactions).
- •Multi-vessel severe disease.
- •Recent acute ST-segment elevation myocardial infarction (STEMI) occurred within 2 weeks prior to randomization.
- •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.
- •Prior treatment with CABG, heart transplantation, SAVR/TAVR, etc., or CABG, heart transplantation, SAVR/TAVR, etc., is required or planned during the study.
- •PCI performed within 4 weeks prior to randomization or PCI is required or planned during study treatment.
- •New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction (LVEF) <40%.
- •Recent clinically evident stroke occurred within 6 months prior to randomization (except for TIA).
- •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 randomization.
- •Evidence of major diseases that not recovered within 2 weeks prior to randomization, or major surgery is expected during the study.
- •Presenting with history of malignancy (except in patients who have been disease-free >5 years; or whose only malignancy has been basal or squamous cell skin carcinoma).
- •Presence of any type of autoimmune disease.
- •Allergy to multiple food or drugs or known sensitivity to any components to be administered during dosing
- •Life expectancy is less than 1 year.
- •Systolic blood pressure of ≥150 mmHg at final screening despite antihypertensive therapy.
- •Known familial hypercholesterolemia
- •Triglycerides≥400 mg/dl (4.5 mmol/l) at final screening.
- •Active liver disease or hepatic dysfunction defined by any of ALT, AST, or total bilirubin > 2 times upper limit of normal (ULN) at final screening.
- •Presence of renal insufficiency.
- •Untreated or inadequately treated hypothyroidism defined by thyroid stimulating hormone (TSH) > 1.5 times ULN at final screening.
- •Poorly controlled (defined by HbA1c > 9%) type 2 diabetes mellitus.
- •A positive hepatitis B surface antigen (HBsAg), or positive antibody against hepatitis C virus (anti-HCV) or human immunodeficiency virus (anti-HIV), or positive treponema pallidum antibody (TP-Ab).
- •Current smoker who has smoked an average of≥5 cigarettes (or equivalent) per day over the preceding year.
- •Presence of any other diseases or conditions (apart from those outlined above) that, in the opinion of the investigator, would make it unsuitable for the patient to participate in this study.
研究组 & 干预措施
Dose 2 treatment arm
Dose 2 YN001 will be administrated intravenously weekly.
干预措施: Evolocumab (Drug)
Dose 1 treatment arm
Dose 1 YN001 will be administrated intravenously weekly.
干预措施: Dose 1 YN001 (Drug)
Dose 1 treatment arm
Dose 1 YN001 will be administrated intravenously weekly.
干预措施: Evolocumab (Drug)
Dose 2 treatment arm
Dose 2 YN001 will be administrated intravenously weekly.
干预措施: Dose 2 YN001 (Drug)
结局指标
主要结局
Changes in coronary plaque characteristics (volume and composition)
时间窗: From baseline to Week 13
Evaluating YN001 on top of evolocumab therapy in changing coronary plaque volume assessed by coronary computed tomography angiography (CCTA).
次要结局
- Change in mean of mean carotid IMT(From baseline to Week 9)
- Change in mean peri-coronary Fat attenuation index (FAI)(From baseline to Week 13)
- The safety profile of YN001(From baseline to Week 15)
- Plasma concentration of total and free drug(From Week 1 to Week 13)
- Population pharmacokinetics (PK)(From Week 1 to Week 13)
- Change in mean of mean carotid IMT(From baseline to Week 13)
- Change in mean of mean carotid IMT(From baseline to Week 5)