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 (2 to Less Than 12 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 9
- 试验地点
- 22
- 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 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) 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 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) 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
- 2 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants, 2 to <12 years of age at screening
- •HoFH diagnosed by genetic confirmation
- •- Note: Participants with known null (negative) mutations in both LDLR alleles are not eligible (see also
排除标准
- •Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
- •On an optimal dose of statin (investigator's discretion), unless statin intolerant, with or without other lipid-lowering therapy (e.g. ezetimibe)
- •Participants on lipid-lowering therapies (such as e.g. statins, ezetimibe) must be on a stable dose for ≥30 days before screening with no planned medication or dose changes during study participation
- •Participants on a documented regimen of LDL-apheresis for ≥ 3 months before screening will be allowed to continue the apheresis during the study, if needed. The apheresis schedule/settings/duration must be stable prior to screening, are not allowed to change during the double-blind period of the trial and must permit that an apheresis coincides with each study visit.
- •Exclusion Criteria:
- •Documented evidence of a null (negative) mutation in both LDLR alleles
- •Previous treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9
- •History of poor response to therapy with any monoclonal antibody directed towards PCSK9 (e.g. <15% reduction in LDL-C)
- •Treatment with mipomersen or lomitapide (within 5 months of screening)
- •Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
- •Heterozygous familial hypercholesterolemia (HeFH)
- •Body weight (at the screening and/or randomization (Day 1) visit) <16 kg for participants 6 to <12 years (at screening) or <11 kg for participants 2 to <6 years (at screening)
- •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
Evaluate the effect of inclisiran compared to placebo on 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)
- Percent change in LDL-C, total cholesterol, non-HDL-C, 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 LDL-C, total cholesterol, non-HDL-C, 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)