A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of AK102 in Patients With Heterozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 109
- 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 heterozygous familial hypercholesterolemia (HeFH).The primary objective of this study is to evaluate the efficacy of AK102 in patients with HeFH.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with heterozygous familial hypercholesterolemia diagnosed by genetic confirmation or clinical diagnosis criteria.
- •Stable on pre-existing, lipid-lowering therapies (statins with or without ezetimibe) for at least 4 weeks with no planned medication or dose change for the duration of study participation.
- •Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 70 mg/dL in patients with history of Atherosclerotic Cardiovascular Disease (ASCVD) or Fasting Low-Density Lipoprotein Cholesterol (LDL-C) ≥ 100 mg/dL in patients without history of Atherosclerotic Cardiovascular Disease (ASCVD).
- •Fasting triglycerides ≤ 400 mg/dL.
- •Body weight ≥ 40kg.
排除标准
- •Subjects with homozygous FH (clinically or by genotyping).
- •Receipt of LDL apheresis within 12 months prior to the first dose of Investigational product.
- •Receipt of Lomitapide or Mipomersen within 5 months prior to the first dose of Investigational product.
- •Prior use of PCSK9 inhibitors.
- •Creatine kinase (CK) >3 times of the upper limit of normal (ULN).
- •Aspartate Aminotransferase (AST) ≥ 2 x ULN.
- •Estimated Glomerular Filtration Rate (eGFR)≤ 30 mL/min/1.73m^
- •Thyroid-Stimulating Hormone (TSH)> 1.5 x ULN or <1 x LLN.
- •Type 1 diabetes, or type 2 diabetes that is or poorly controlled（HbA1c> 8.5%).
- •Subjects with untreated or active chronic hepatitis B or active hepatitis C virus infections.
研究组 & 干预措施
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)
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: Placebo (Drug)
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks
干预措施: Statins and/or Ezetimibe (Drug)
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks
干预措施: Placebo (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 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)
- 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)
- Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9)(From baseline through 12 weeks)
- Percent change from baseline in low-density lipoprotein cholesterol (LDL-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)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(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 Apolipoprotein B (Apo B)(From baseline through 12 weeks)