Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Adolescents (12 to Less Than 18 Years) With Heterozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-16)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 141
- 试验地点
- 78
- 主要终点
- Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)
研究概览
简要总结
This was a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C).
详细描述
This was a two-part (1 year double-blind inclisiran versus placebo / 1 year open-label inclisiran) multicenter study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy. The primary objective was to demonstrate superiority of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.
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)
盲法说明
Masked (Year 1) to No Masking (Year 2)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Heterozygous Familial Hypercholesterolemia (HeFH) diagnosed either by genetic testing or on phenotypic criteria
- •Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
- •Fasting triglycerides <400 mg/dL (4.5 mmol/L) at screening
- •On maximally tolerated dose of statin (investigator's discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening
排除标准
- •Homozygous familial hypercholesterolemia (HoFH)
- •Active liver disease
- •Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
- •Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
- •Recent and/or planned use of other investigational medicinal products or devices
研究组 & 干预措施
Inclisiran
Year 1 - inclisiran sodium 300 mg subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 450 and 630)
干预措施: Inclisiran (Drug)
Placebo
Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 360, 450, and 630)
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage Change in LDL-C From Baseline to Day 330 (Part 1/Year 1)
时间窗: Baseline and Day 330
Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)
次要结局
- Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 330 (Part 1/Year 1)(Baseline, after Day 90 up to Day 330)
- Absolute Change in LDL-C From Baseline to up Day 330 (Part 1/Year 1)(Baseline and Day 330)
- Percent Change in Apo B From Baseline up to Day 330 (Part 1/Year 1)(Baseline and Day 330)
- Percent Change in Lp(a) From Baseline up to Day 330 (Part 1/Year 1)(Baseline and Day 330)
- Percent Change in Non-HDL-C From Baseline up to Day 330 (Part 1/Year 1)(Baseline and Day 330)
- Percent Change in Total Cholesterol From Baseline up to Day 330 (Part 1/Year 1)(Baseline and Day 330)
- Percent Change in LDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in LDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in Apo B From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in Apo B From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in Lp(a) From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in Lp(a) From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in Non-HDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in Non-HDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in Total Cholesterol From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in Total Cholesterol From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in Triglycerides From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in Triglycerides From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in HDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in HDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in VLDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Absolut Change in VLDL-C From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in Apo A1 From Baseline up to Day 720(Baseline, up to Day 720)
- Absolute Change in Apo A1 From Baseline up to Day 720(Baseline, up to Day 720)
- Percent Change in PCSK9 From Baseline up to Day 720(Baseline, up to Day 720)
- Absolut Change in PCSK9 From Baseline up to Day 720(Baseline, up to Day 720)