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奥拉西壬临床试验的设计与原理——心血管事件和脂蛋白(a)降低剂量发现研究(OCEAN(a)-DOSE)。

Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE).

机构信息

TIMI Study Group, Brigham and Women's Hospital, Boston, MA.

Global Development, Amgen, Thousand Oaks, CA.

出版信息

Am Heart J. 2022 Sep;251:61-69. doi: 10.1016/j.ahj.2022.05.004. Epub 2022 May 16.


DOI:10.1016/j.ahj.2022.05.004
PMID:35588897
Abstract

BACKGROUND: Data support lipoprotein(a) (Lp[Lp(a)]) being a risk factor for atherosclerotic cardiovascular disease (ASCVD). Olpasiran is a small interfering RNA molecule that markedly reduces Lp(a) production in hepatocytes. STUDY DESIGN: The Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study is a multicenter, randomized, double-blind, placebo-controlled dose-finding study in 281 subjects with established ASCVD and Lp(a) > 150 nmol/L. Patients were randomly allocated to one of 4 active subcutaneous doses of olpasiran (10 mg q12 weeks, 75 mg q12 weeks, 225 mg q 12 weeks, or 225 mg q24 weeks) or matched placebo. The primary objective is to evaluate the effects of olpasiran dosed every 12 weeks compared with placebo on the percent change in Lp(a) from baseline at 36 weeks. Enrollment is now complete and follow-up is ongoing. CONCLUSIONS: OCEAN(a)-DOSE trial is assessing the Lp(a)-lowering efficacy and safety of olpasiran. These data will be used to determine optimal dosing and design for a cardiovascular outcomes trial.

摘要

背景:数据支持脂蛋白(a)(Lp[a])是动脉粥样硬化性心血管疾病(ASCVD)的一个风险因素。Olpasiran 是一种小干扰 RNA 分子,可显著减少肝细胞中 Lp(a)的产生。 研究设计:心血管事件和脂蛋白(a)降低剂量发现研究的 Olpasiran 试验是一项多中心、随机、双盲、安慰剂对照的剂量发现研究,纳入了 281 例有明确 ASCVD 且 Lp(a)>150nmol/L 的患者。患者被随机分配至以下 4 种皮下注射的 olpasiran 活性剂量组之一(10mg q12 周、75mg q12 周、225mg q12 周或 225mg q24 周)或匹配的安慰剂组。主要目的是评估每 12 周给药的 olpasiran 与安慰剂相比,在 36 周时对 Lp(a)从基线的百分比变化的影响。目前已完成入组,正在进行随访。 结论:OCEAN[a]-DOSE 试验正在评估 olpasiran 降低 Lp(a)的疗效和安全性。这些数据将用于确定心血管结局试验的最佳剂量和设计。

相似文献

[1]
Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE).

Am Heart J. 2022-9

[2]
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[3]
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[4]
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[5]
Pharmacokinetics, Pharmacodynamics, and Tolerability of Olpasiran in Healthy Japanese and Non-Japanese Participants: Results from a Phase I, Single-dose, Open-label Study.

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[6]
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[7]
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[10]
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[3]
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[4]
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[5]
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[6]
Lipoprotein (a) levels and clinical decision-making: data from a Mexican cohort at a tertiary medical institution.

Lipids Health Dis. 2025-5-26

[7]
Recent Update on siRNA Therapeutics.

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[8]
Causal Relevance of Lp(a) for Coronary Heart Disease and Stroke Types in East Asian and European Ancestry Populations: A Mendelian Randomization Study.

Circulation. 2025-4-29

[9]
Lipoprotein(a) and Atrial Fibrillation: Mechanistic Insights and Therapeutic Approaches.

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[10]
Increasing provider awareness of Lp(a) testing for patients at risk for cardiovascular disease: A comparative study.

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