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 Children (6 to Less Than 12 Years) With Heterozygous Familial Hypercholesterolemia and Elevated LDL- Cholesterol
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 74
- 主要终点
- Percentage change in LDL-C from baseline to Day 330 (Year 1)
研究概览
简要总结
This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 6 to <12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDLC).
详细描述
This is 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 children (aged 6 to <12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy.
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
- 6 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants, 6 to <12 years of age at screening
- •HeFH diagnosed either by genetic testing or on phenotypic criteria
- •Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
- •For participants 8 to <12 years, on an optimal dose of statin (investigator's discretion) unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe). For participants <8 years, the use of background lipid-lowering treatment is based on investigator's discretion.
- •Participants on lipid-lowering therapies (such as statin and/or e.g. ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation.
排除标准
- •Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
- •Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
- •Homozygous familial hypercholesterolemia (HoFH)
- •Body weight <16 kg at the screening and/or randomization (Day 1) visit
- •Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except patients with Gilbert's syndrome)
- •Pregnant or nursing females
- •Recent and/or planned use of other investigational medicinal products or devices
研究组 & 干预措施
Placebo
Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium subcutaneous injection (given at Days 360, 450, and 630)
干预措施: Placebo (Drug)
Inclisiran
Year 1 - inclisiran sodium subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium subcutaneous injection (given at Days 450 and 630)
干预措施: Inclisiran (Drug)
结局指标
主要结局
Percentage change in LDL-C from baseline to Day 330 (Year 1)
时间窗: Baseline and Day 330
Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C \[percent change\] at Day 330
次要结局
- Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Year 1)(Baseline, after Day 90 up to Day 330)
- Absolute change in LDL-C from baseline to Day 330 (Year 1)(Baseline and Day 330)
- Percent change in PCSK9 from baseline to Day 330 (Year 1)(Baseline and Day 330)
- Percent change in total cholesterol, non-HDL-C from baseline to Day 330 (Year 1)(Baseline and Day 330)
- Percent change in Apo B from baseline to Day 330 (Year 1)(Baseline and Day 330)
- Percent change in LDLC, total cholesterol, non-HDLC, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)
- Percent change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)
- Percent change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)
- Absolute change in LDLC, total cholesterol, non-HDLC, triglycerides, HDL-C, VLDL-C from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)
- Absolute change in PCSK9 from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)
- Absolute change in Apo B, Apo A1 from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)
- Percent change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)
- Absolute change in Lp(a) from baseline to each assessment time up to Day 720 (Year 2)(Baseline, up to Day 720)