A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Followed by an Open-Label Continuation Period to Assess the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 309
- 主要终点
- Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1
研究概览
简要总结
Primary objective:
Determine whether mipomersen (ISIS 301012) significantly reduces atherogenic lipid levels in patients with severe heterozygous familial hypercholesterolemia (severe HeFH), defined as low-density lipoprotein cholesterol (LDL-C) levels ≥200 mg/dL plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels ≥300 mg/dL regardless of the presence of CHD/risk equivalents (referred to as Cohort 1) compared to placebo. Two different mipomersen dosing regimens will be studied: subcutaneous (SC) mipomersen 200 mg once weekly versus placebo, and SC mipomersen 70 mg thrice weekly versus placebo.
Secondary Objectives:
- Determine whether there are qualitative differences between the safety profiles of the 2 dosing regimens and placebo in Cohort 1, patients with HeFH with LDL-C levels ≥160 mg/dL and <200 mg/dL plus the presence of CHD/risk equivalents (referred to as Cohort 2), and the overall study population
- Determine whether there are qualitative differences between the tolerability of the 2 dosing regimens and placebo in Cohort 1, Cohort 2, and the overall study population
- Further characterize the pharmacokinetics (PK) of the 2 dosing regimens in Cohort 1, Cohort 2, and the overall study population
- Determine whether the 2 mipomersen dosing regimens significantly reduce atherogenic lipid levels in Cohort 2 compared to placebo
- Obtain additional data regarding ongoing safety and efficacy of mipomersen in patients with FH and inadequately controlled LDL-C who complete the primary efficacy assessment visit (PET) in the Blinded Treatment Period and continue treatment in Open-Label Continuation Period
详细描述
The study consisted of a Screening period of up to 4 weeks, Blinded Treatment Phase of 60 weeks, Open-Label Continuation Period of 26 weeks, and Post-Treatment Phase of 24 weeks.
Study Design, masking - Study treatment was blinded (double-blinded) through the Primary Efficacy Assessment Visit in the Blinded Treatment Period. Study treatment was open-label in the Open-Label Continuation Period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Diagnosis of severe hypercholesterolemia (LDL-C ≥300 mg/dL (7.77 mmol/L) or LDL-C ≥200 mg/dL (5.18 mmol/L) with documented coronary heart disease (CHD) or CHD risk equivalents, or diagnosis of Heterozygous Familial Hypercholesterolemia and LDL-C ≥160 mg/dL (4.14 mmol/L) and <200 mg/dL (5.18 mmol/L))
- •On stable, maximally tolerated, statin therapy for at least 12 weeks or if statin intolerant, on at least 1 medication from another class of hypolipidemic agents (i.e., bile acid sequestrants, niacin/nicotinic acid, cholesterol absorption inhibitors, fibrates).
- •On stable, low fat diet for 12 weeks
- •Body mass index (BMI) ≤40 kg/m2 and stable weight for > 6 weeks
排除标准
- •Significant health problems in the recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, hypertension, blood disorders, liver disease, cancer, digestive disorders, Type I diabetes, or uncontrolled Type II diabetes
- •Apheresis within 3 months prior to Screening or expected to start apheresis during the treatment phase
研究组 & 干预措施
Regimen B: Placebo
Placebo matching subcutaneous injection thrice weekly.
干预措施: Placebo (Drug)
Regimen A: Mipomersen
Subcutaneous injection of mipomersen 200 mg once weekly
干预措施: mipomersen sodium 200 mg (Drug)
Regimen A: Placebo
Placebo matching subcutaneous injection once weekly.
干预措施: Placebo (Drug)
Regimen B: Mipomersen
Subcutaneous injection of mipomersen 70 mg thrice weekly.
干预措施: mipomersen sodium 70 mg (Drug)
结局指标
主要结局
Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1
时间窗: Baseline and Week 61
The percent change from baseline to PET in LDL-C was measured in Cohort 1, which included participants with severe heterozygous familial hypercholesterolemia (HeFH). Severe HeFH was defined as LDL-C levels ≥200 mg/deciliter (dL) plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels ≥300 mg/dL regardless of the presence of CHD/risk equivalents.
次要结局
- Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1(Baseline and Week 61)
- Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2(Baseline and Week 61)
- Percent Change From Baseline To PET In LDL-C In Cohort 2(Baseline, PET (up to 60 weeks))
- Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1(Baseline and Week 61)
- Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2(Baseline and Week 61)