A Study to Evaluate Safety and Efficacy of IBI306 in Patients With Heterozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 149
- 试验地点
- 1
- 主要终点
- Percentage of LDL-C decreased from baseline injection.
研究概览
简要总结
IBI306 is a fully human monoclonal antibody that binds proprotein convertase substilisin/kexin type 9 (PCSK-9), preventing its interaction with the low-density lipoprotein cholesterol receptor (LDL-R) and thereby restoring LDL-R recycling and low-density lipoprotein cholesterol (LDL-C) uptake. In the phase I study, IBI306 was shown to be safe and well tolerated. There was robust reduction in LDL-C, Apo(B), non-HDL-C and lipoprotein (a) in healthy subjects. This study is a randomized, double-blind, placebo-controlled, repeated-dosing, multiple ascending dose trial to evaluate the efficacy and safety of a novel PCSK-9 anti-body, IBI306, in Chinese patients with heterozygous familial hypercholesterolemia.
详细描述
The study plans to enroll 148 patients with heterozygous familial hypercholesterolemia. Subjects will maintain a low-fat diet and stable current lipid-lowering therapy for at least 4 weeks and will be randomized into different dose groups at a 1:1 ratio, followed by a 2:1 randomization double-blind treatment with subcutaneous IBI306 150 mg (n=49) or placebo (n=25) every two weeks; or subcutaneous injection of IBI306 450mg (n=49) or placebo (n=25) every four weeks. Treatment lasts for 12 weeks. After 12 weeks, each group enters a 12-week open-label treatment, in which IBI306 subjects continue to receive IBI306, and placebo subjects shift to receive IBI306. The primary endpoint is the percent change in LDL-C levels relative to baseline at 12 weeks. Secondary endpoints include changes in baseline lipid levels, drug safety, and immunogenicity at 12 weeks and 24 weeks. The exploratory endpoint is the population pharmacokinetic profile of IBI306 in Chinese subjects with heterozygous familial hypercholesterolemia. If necessary, the dose of IBI306 will be adjusted accordingly based on the results of the ongoing multi-dose escalation study. After the open period, the subjects will be given a safety visit for 8 weeks.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must meet all of the following inclusion criteria in order to be included in the study:
- •Provide a signed and dated informed consent form
- •Men or women 18 to 70 years of age at screening
- •Weight ≥ 40 kg during screening
- •Confirmed diagnosis of heterozygous familial hypercholesterolemia
- •Maintain a low-fat diet and stabilize the current lipid-lowering therapy
排除标准
- •Subjects who do not meet any of the following exclusion criteria cannot be included in the study:
- •Patients diagnosed as homozygous familial hypercholesterolemia
- •Dialysis or plasmapheresis performed within 4 months prior to screening
- •History of liver transplant
- •Subjects adjusted for treatment of statins, ezetimibe, niacin, omega-fatty acids within 4 weeks prior to screening
- •New York Heart Association (NYHA) grade III or IV heart failure, or recent detection of left ventricular ejection fraction ≤ 30%
- •Have serious cardiovascular, cerebrovascular, liver and kidney related diseases
研究组 & 干预措施
IBI306
Participants received IBI306 150 mg subcutaneously Q2W or 450mg Q4W for 12 weeks.
干预措施: IBI306 (Drug)
placebo
Participants received Placebo 150 mg subcutaneously Q2W or 450mg Q4W for 12 weeks.
干预措施: placebo (Drug)
结局指标
主要结局
Percentage of LDL-C decreased from baseline injection.
时间窗: at 12 weeks
次要结局
- Changes in LDL-C levels relative to baselin(at 12 and 24 weeks)
- Percentage change of LDL-C from baseline(to 24 weeks)
- The proportion of patients with LDL-C that were 50% lower than baseline(by 12 weeks and 24 weeks)