An Open-Label Extension Study to Assess the Long-term Safety and Efficacy of Mipomersen in Subjects With Familial Hypercholesterolemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 主要终点
- Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of extended dosing of mipomersen in patients with familial hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) clinical drug trials.
详细描述
Familial Hypercholesterolemia (FH) is an autosomal dominant metabolic disorder characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis, and development of xanthomata. There are two distinct subpopulations that have a high unmet medical need due to the lack of alternative therapy: homozygotes, who have two defective LDL receptor (LDL-R) genes, and heterozygotes with a history of cardiovascular disease (CVD) on maximally tolerated therapy. Treatment for FH is directed at lowering plasma levels of LDL-C.
Mipomersen is an antisense drug targeted to human apolipoprotein B (apoB), the principal apolipoprotein of atherogenic LDL-C and its metabolic precursor, very low density lipoprotein (VLDL). Mipomersen is complimentary to the coding region of the messenger ribonucleic acid (mRNA) for apo-B. Inhibition of apo-B would be expected to impair VLDL synthesis and result in lowered levels of LDL-C.
In early clinical trials, mipomersen has been shown to reduce levels of LDL-C to recommended target levels in some participants.
This was an open-label extension study, which consisted of a ≤2-week screening period, up to 3 years of treatment with mipomersen, and a 24-week post-treatment follow-up period. Patients who participated in Cohorts A, B, or C in study 301012-CS9 were randomized in a 1:1 ratio to mipomersen 200 mg once a week (QW) or 200 mg mipomersen every other week (QOW) for up to 3 years. Patients randomized to mipomersen 200 mg QOW were allowed to receive mipomersen 200 mg QW at the Investigator's discretion after the first 52 weeks of the treatment period. Patients who participated in study 301012-CS8 or Cohort D of study 301012-CS9 received 200 mg mipomersen QW for up to 3 years.
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
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Satisfactory completion of dosing and Week 7 or Week 15 assessments (depending on the treatment and dose received) in their initial study (Protocol 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008)).
排除标准
- •Have a new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with patient's participation in or completion of the study.
研究组 & 干预措施
Mipomersen 200 mg per week
Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years.
干预措施: mipomersen sodium (Drug)
Mipomersen 200 mg every other week
Participants received 200 mg mipomersen every other week by subcutaneous injection, for up to 3 years. Participants could receive mipomersen 200 mg once a week at the Investigator's discretion after the first 52 weeks of the treatment period.
干预措施: mipomersen sodium (Drug)
结局指标
主要结局
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
时间窗: Baseline and Weeks 52 and 104
LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Low-density Lipoprotein Cholesterol (LDL-C) Over Time
时间窗: Baseline and Weeks 52 and 104.
Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
次要结局
- Apolipoprotein B Over Time(Baseline and Weeks 52 and 104.)
- Total Cholesterol Over Time(Baseline and Weeks 52 and 104.)
- Percent Change From Baseline in Respiratory Rate(Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.)
- Number of Participants With Treatment-Emergent Adverse Events (AEs)(2 years)
- Percent Change From Baseline in Total Cholesterol(Baseline and Weeks 52 and 104.)
- Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol(Baseline and Weeks 52 and 104.)
- Percent Change From Baseline in Clinical Chemistry Parameters(Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.)
- Percent Change From Baseline in Apolipoprotein B(Baseline and Weeks 52 and 104)
- Percent Change From Baseline in Hematology Parameters(Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment)
- Percent Change From Baseline in Blood Pressure(Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.)
- Non-High-Density Lipoprotein Cholesterol Over Time(Baseline and Weeks 52 and 104.)
- Percent Change From Baseline in Pulse Rate(Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.)