An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 144
- 主要终点
- Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
研究概览
简要总结
To evaluate the safety and efficacy of extended dosing with mipomersen (ISIS 301012) in participants with familial hypercholesterolemia or severe hypercholesterolemia on lipid-lowering therapy who had completed either the 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849), 301012-CS17 (NCT00477594) or MIPO3500108 (NCT00794664) clinical drug trials.
详细描述
All familial hypercholesterolemia (FH) or severe hypercholesterolemia participants who had tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 were eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen was commercially available, whichever comes first. Consenting participants who had tolerated mipomersen and satisfactorily completed 301012-CS17 (NCT00477594) through Year 3 may also enroll for up to an additional 2 years of treatment in this study or until mipomersen was commercially available, whichever comes first. All participants, who entered the study, received 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Participants who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weighed <50 kg received 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) were allowed for participants who were not tolerating or who had previous issues with tolerating the once a week injections due to injection site reactions (ISRs) or flu-like symptoms. Study visits and clinical lab assessments including hematology with differential, chemistry, serum lipid panel (total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), apoA-1, triglycerides (TG) and Lp(a), and urinalysis was to be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels was to be measured to estimate exposure. Participants who completed dosing or who discontinued prematurely from the study for any reason was followed for safety for 24 weeks (safety follow-up period) after their last dose of mipomersen (ISIS 301012) or longer in the case of a significant adverse events (AE) or abnormal biochemical or clinical finding. Participants were required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 in their initial study (Protocol 301012-CS5 [NCT00607373], 301012-CS7 [NCT00706849], 301012-CS17 [NCT00477594], or MIPO3500108 [NCT00794664])
排除标准
- •Had any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
研究组 & 干预措施
Mipomersen
Mipomersen Sodium once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
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 up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
时间窗: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Percent Change From Baseline in Apolipoprotein B (Apo B)
时间窗: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Percent Change From Baseline in Total Cholesterol
时间窗: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
次要结局
- Percent Change From Baseline in HDL Particles' Size (Small)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in VLDL Particles' Size (Medium)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Change From Baseline in C-Reactive Protein(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in Triglycerides(Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in LDL Particles' Size (Total)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in LDL Particles' Size (Small)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in LDL Particles' Size (Very Small)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in Lipoprotein (a)(Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in LDL Particles' Size (Large)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in LDL Particles' Size (Medium)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in HDL Particles' Size (Medium)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in Apolipoprotein A-1(Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in HDL Particles' Size (Large)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))
- Percent Change From Baseline in VLDL Particles' Size (Small)(Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years))