A Double-blind, Randomized, Placebo-controlled, Multicenter Phase II Study of AK102 in the Treatment of Hypercholesterolemia Patients at Very High or High Risk of Cardiovascular Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 262
- 试验地点
- 2
- 主要终点
- Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
研究概览
简要总结
This is a double-blind, randomized, placebo-controlled, multicenter study to evaluate the safety and efficacy of AK102 in patients with Hypercholesterolemia Patients at Very High or High Risk of Cardiovascular Disease .
The primary objective of this study is to evaluate the efficacy of AK102 in patients with Hypercholesterolemia Patients at Very High or High Risk of Cardiovascular Disease .
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, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent form (ICF), and be able to comply with the treatment plan, visit, laboratory examination and other requirements specified in the study;
- •Age ≥ 18, male or female;
- •According to the guidelines for the prevention and treatment of dyslipidemia in Chinese adults (revised in 2016), subjects assessed as very high risk or high risk of cardiovascular disease;
- •Subjects received stable and optimal dose of statins for at least 4 weeks before randomization, either in combination with or without ezetimibe;
- •The blood lipid level of the patients with stable 4-week basic lipid-lowering drug treatment met one of the following conditions by the central laboratory test: LDL-C level in very high risk subjects > 1.8 mmol / L (70 mg / dl) or LDL-C level of high-risk subjects > 2.6 mmol / L (100 mg / dl)
- •TG ≤ 4.5 mmol / L (400 mg / dl) measured by central laboratory at screening；
排除标准
- •Has received cholesterol ester transfer protein (CETP) inhibitor within12 months prior to randomization;
- •Has received PCSK9 inhibitors or are known to be allergic to PCSK9 inhibitors or their components;
- •Has received other investigational drugs within 4 weeks or within 5 half lives (whichever was longer) prior to screening.
- •Has previously received biological agent treatment, organ transplantation or gene therapy;
- •Abnormal laboratories prior to the first study drug administration: ALT or AST> 3 × ULN; Creatine kinase > 5 × ULN; eGFR <= 30 ml/min/1.73m2 by Cockcroft Gault method;
- •Uncontrolled hypothyroidism or hyperthyroidism defined as TSH < 1.0 ×LLN or > 1.5 × ULN, respectively;
- •Myocardial infarction, unstable angina pectoris, percutaneous coronary intervention (PCI), coronary bypass grafting (CABG), stroke, severe deep vein thrombosis or pulmonary embolism, or severe arrhythmia occurred within three months prior to randomization ;
- •Grade III or IV according to NYHA assessment;
- •Planned to have heart-related surgery within 3 months after randomization;
- •Type 1 diabetes or poorly controlled type 2 diabetes [HbA1c > 8.5% within 1 month];
- •Subjects with hypertension that could not be controlled by drugs;
- •Known concomitant diseases that may lead to secondary hyperlipidemia, including nephrotic syndrome, cholestatic liver failure, etc;
- •Positive HBsAg or HCV antibody;
- •Known history of primary immunodeficiency virus infection or positive human immunodeficiency virus (HIV) test;
- •History of drug or alcohol abuse prior to screening;
- •Has taken the following drugs within 6 weeks prior to screening: red koji rice > 200 mg/day; niacin > 1000 mg/day; omega-3 fatty acids; steroids or prescription lipid regulating drugs ; cholesterol lowering drugs, health care products, Chinese patent medicines or other food additives other than statins and ezetimibe;
- •Has taken the following drugs within 3 months prior to screening: systemic cyclosporine, systemic steroids, vitamin A derivatives and retinol derivatives for the treatment of skin diseases (such as retinoic acid).
研究组 & 干预措施
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: Statins and/or Ezetimibe (Drug)
AK102 450 mg
Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: AK102 (Drug)
AK102 450 mg
Participants received AK102 450 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: Statins and/or Ezetimibe (Drug)
AK102 300 mg
Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: AK102 (Drug)
AK102 300 mg
Participants received AK102 300 mg subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: Statins and/or Ezetimibe (Drug)
AK102 150 mg
Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
干预措施: AK102 (Drug)
AK102 150 mg
Participants received AK102 150 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
干预措施: Statins and/or Ezetimibe (Drug)
AK102 75 mg
Participants received AK102 75 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
干预措施: AK102 (Drug)
AK102 75 mg
Participants received AK102 75 mg subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
干预措施: Statins and/or Ezetimibe (Drug)
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: Placebos (Drug)
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
干预措施: Placebos (Drug)
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
干预措施: Statins and/or Ezetimibe (Drug)
结局指标
主要结局
Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at Week 12
时间窗: At baseline and week 12
次要结局
- Percent change from baseline in low-density lipoprotein cholesterol (LDL-C)(From baseline through 12 weeks)
- Percent change from baseline in high-density lipoprotein cholesterol (HDL-C)(From baseline through 12 weeks)
- Percent change from baseline in non High-density lipoprotein (non-HDL) cholesterol(From baseline through 12 weeks)
- Percent change from baseline in serum Triglyceride (TG) cholesterol(From baseline through 12 weeks)
- Percent change from baseline in Apolipoprotein B (Apo B)(From baseline through 12 weeks)
- Percent change from baseline in Apolipoprotein A-I (ApoA-I)(From baseline through 12 weeks)
- Percent change from baseline in Lipoprotein(a) [Lp-(a)](From baseline through 12 weeks)
- Percent change from baseline in Total Cholesterol(TC)(From baseline through 12 weeks)
- Incidence of treatment-emergent adverse events(From baseline through 12 weeks)
- Serum concentrations of AK102(From baseline through 12 weeks)
- Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)(From baseline through 12 weeks)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From baseline through 12 weeks)