An Open-Label, Single-Arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of ALN-PCSSC in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 3
- 主要终点
- Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, and efficacy of ALN-PCSSC in participants with homozygous familial hypercholesterolemia.
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
- •Males and females, ≥12 years of age with a diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated low-density lipoprotein cholesterol (LDL-C) concentration >500 mg/deciliter (dL) [13 millimoles/liter (mmol/L)] together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents.
- •Stable on a low-fat diet.
- •Stable on pre-existing, lipid-lowering therapies (such as statins, cholesterolabsorption inhibitors, bile-acid sequestrants, or combinations thereof) for at least 4 weeks with no planned medication or dose change for the duration of study participation.
- •Fasting central lab LDL-C concentration >130 mg/dL (3.4 mmol/L) and triglyceride concentration <400 mg/dL (4.5 mmol/L).
- •Body weight of 40 kilograms (kg) or greater at screening.
排除标准
- •LDL or plasma apheresis within 8 weeks prior to the screening visit, and no plan to receive it during the study because of the attendant difficulty in maintaining stable concentrations of LDL-C while receiving apheresis.
- •Use of mipomersen or lomitapide therapy within 5 months of screening.
- •Previous treatment with monoclonal antibodies directed towards PCSK9 within 8 weeks of screening.
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
ALN-PCSSC
300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy.
干预措施: Standard of Care (Drug)
ALN-PCSSC
300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy.
干预措施: ALN-PCSSC (Drug)
结局指标
主要结局
Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C
时间窗: Day 1, Day 180 (or Final Visit)
Percentage Change From Day 1 to Day 90 in LDL-C
时间窗: Day 1, Day 90
Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented.
次要结局
- Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9(Day 1, Day 60, Day 90)
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9(Day 1, Day 60, Day 90)
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B(Day 1, Day 90, Day 180 (or Final Visit))
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a(Day 1, Day 90, Day 180 (or Final Visit))
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides(Day 1, Day 90, Day 180 (or Final Visit))
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C(Day 1, Day 90, Day 180 (or Final Visit))
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1(Day 1, Day 90, Day 180 (or Final Visit))
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1(Day 1, Day 90, Day 180 (or Final Visit))
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C(Day 1, Day 90, Day 180 (or Final Visit))
- Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C(Day 1, Day 90, Day 180 (or Final Visit))
- Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C(Day 1, Day 90, Day 180 (or Final Visit))