一次上升和多次剂量的Zerlasiran试验,一个短干扰RNA向脂蛋白:一个随机临床试验
Steven E Nissen1, Kathy Wolski1, Gerald F Watts2
1Cleveland Clinic Center for Clinical Research, Cleveland, Ohio.
JAMA
|April 8, 2024
概括
泽拉西兰是一种新型RNA疗法,有效降低了动脉样硬化心血管疾病患者的脂蛋白水平. 这种治疗耐受性很好,为控制心血管风险提供了一个有前途的新选择.
科学领域:
- 心血管医学
- 药理学
- 遗传学和分子生物学
背景情况:
- 脂蛋白 (a) 是动脉样硬化心血管疾病 (ASCVD) 和动脉狭窄症的重要基因风险因素.
- 目前管理高脂蛋白水平的治疗选择有限,突出显示需要新的药物干预措施.
- 使用短干扰RNA (siRNA) 技术向肝脏的阿波脂蛋白合成.
研究的目的:
- 在健康参与者和稳定的ASCVD患者中评估泽拉西兰的安全性和耐受性.
- 评估泽拉西兰对血清脂蛋白度的影响.
- 确定不同剂量方案的疗效.
主要方法:
- 一期随机单剂和多剂量研究,涉及健康志愿者和ASCVD患者,脂蛋白水平高 (> 150nmol/ l).
- 参与者通过皮下注射接受安慰剂或不同剂量的泽拉西兰.
- 监测了安全性,耐受性,血清泽拉西兰度和脂蛋白度.
主要成果:
- 泽拉西兰表现出良好的安全性和耐受性,没有报告严重的不良反应.
- 单剂量泽拉西兰导致脂蛋白水平显著降低 (高达30%的300毫克).
- 多次剂量导致脂蛋白的显著和持续减少,最大的中位数变化高达99%.
结论:
- 泽拉西兰是一种耐受性良好的siRNA治疗药物,有效降低高脂蛋白度.
- 对与高脂蛋白相关的心血管风险的长期管理有希望.
- 这些发现支持在更大规模的临床试验中对泽拉西兰进行进一步的研究以预防ASCVD.
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