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 Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-13)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 15
- 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 homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C).
详细描述
This was a two-part (double-blind, inclisiran versus placebo [Year 1] followed by open-label inclisiran [Year 2]) multicenter study in adolescents (aged 12 to < 18 years) with HoFH and elevated LDL-C (> 130 mg/dL; 3.4 mmol/L) on stable, individualized, optimal standard of care (SoC) background lipid-lowering therapy (including maximally tolerated statin treatment, at the Investigator's discretion) to evaluate the safety, tolerability, and efficacy of inclisiran in this pediatric patient population.
Following an approximately 4-week screening/run-in period, the study had 2 sequential parts as follows:
Part 1/Year 1: 12 months double-blind, parallel group period, in which participants were randomized in a 2:1 ratio to receive either inclisiran sodium 300 mg subcutaneous (s.c.) or placebo. The primary endpoint was assessed at Day 330.
Part 2/Year 2: 12 months single arm, open-label follow-up period, with all participants receiving inclisiran sodium 300 mg s.c.
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
- •Homozygous Familial Hypercholesterolemia (HoFH) diagnosed by genetic confirmation
- •Fasting LDL-C >130 mg/dL (3.4 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
- •Male or female participants >=12 to <18 years of age at screening
排除标准
- •Documented evidence of a null (negative) mutation in both LDLR alleles
- •Heterozygous familial hypercholesterolemia (HeFH)
- •Active liver disease
- •Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
- •Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
- •Treatment with mipomersen or lomitapide (within 5 months of screening)
- •Recent and/or planned use of other investigational medicinal products or devices
研究组 & 干预措施
Part 1 - Inclisiran
Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
干预措施: Inclisiran (Drug)
Part 1 - Placebo
Placebo sc injection (given at Day 1, 90 and 270)
干预措施: Placebo (Drug)
Part 2 - Inclisiran (Total)
Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360.
干预措施: Inclisiran (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
- 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)
- 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)
- 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)