A Multi-centre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study to Investigate Efficacy, Safety and Tolerability of SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 29
- 主要终点
- Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36
研究概览
简要总结
Phase 2 study to evaluate the efficacy, safety and tolerability of SLN360 administered subcutaneously (SC) compared with placebo in adult participants with elevated lipoprotein(a) at high risk of atherosclerotic cardiovascular disease events
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)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Lipoprotein(a) at screening equal to or greater than 125 nmol/L
- •At high risk of ASCVD events
- •A body mass index at screening in the range of 18.0 to 32.0 kg/m², inclusive
排除标准
- •Renal dysfunction with estimated glomerular filtration rate less than 30 mL/min/1.73 m² at screening
- •History or clinical evidence of hepatic dysfunction
- •Malignancy within the 5 years before screening
- •Fasting triglycerides >400 mg/dL (4.5 mmol/L) at screening
- •Currently receiving or <12 weeks at Day 1 since receiving >200 mg/day niacin or niacin derivative drugs
- •Treatment with lipid/lipoprotein apheresis within the 12 weeks before screening
- •Any previous use of approved or experimental small interfering RNA (siRNA) therapy (e.g. inclisiran). NB: use of messenger RNA (mRNA) based vaccines for infectious diseases is permitted
研究组 & 干预措施
SLN360 300 mg Q16W
SLN360 300 mg administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
干预措施: SLN360 (Drug)
SLN360 300 mg Q24W
SLN360 300 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
干预措施: SLN360 (Drug)
SLN360 450 mg Q24W
SLN360 450 mg administered subcutaneously at Weeks 0 and 24 (Q24W)
干预措施: SLN360 (Drug)
Placebo Q16W
Placebo administered subcutaneously at Weeks 0, 16 and 32 (Q16W)
干预措施: Placebo (Drug)
Placebo Q24W
Placebo administered subcutaneously at Weeks 0 and 24 (Q24W). This group was stratified so that half of participants were dosed to match the SLN360 300 mg Q24W group and half were dosed to match the SLN360 450 mg Q24W group (with respect to injected volume)
干预措施: Placebo (Drug)
结局指标
主要结局
Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 36
时间窗: Week 36
Clinical trial results (relative to Day 1 pre-dose) was calculated for each participant by estimating the sum of the area under the curve with the linear trapezoidal method for all scheduled assessments from Week 4 to Week 36, inclusive, divided by the total time interval between the Week 4 and Week 36 assessments. Analysis of variance was used to test for differences between each active treatment group and the pooled placebo groups in the primary outcome measure. Time-averaged percent change in lipoprotein(a) to Week 36 was the dependent variable, and treatment group was included as the predictor variable. The least squares means, standard errors, and 2-sided 95% confidence intervals for each treatment group and for the pairwise comparisons between the SLN360 and placebo groups were estimated.
次要结局
- Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 48(Week 48)
- Time-averaged Percent Change In Lipoprotein(a) Molar Concentration From Baseline to Week 60(Week 60)
- Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 36(Week 36)
- Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 48(Week 48)
- Time-averaged Percent Change In Apolipoprotein B Concentration From Baseline to Week 60(Week 60)
- Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 36(Week 36)
- Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 48(Week 48)
- Time-averaged Percent Change In Low-density Lipoprotein Cholesterol Concentration From Baseline to Week 60(Week 60)