Patients with kidney failure on hemodialysis (KF-HD) are at high risk for both atherothrombotic events and bleeding. This Phase IIb study evaluated the dose-response of fesomersen, an inhibitor of hepatic Factor XI expression, placebo, for bleeding and atherothrombosis in patients with KF-HD. Patients were randomized to receive fesomersen 40, 80, or 120 mg once-monthly, or matching placebo, for up to 12 months. The primary safety endpoint was a composite of major bleeding and clinically relevant non-major bleeding (MB/CRNMB). Exploratory endpoints included post-dialysis arterio-venous (AV)-access bleeding, major atherothrombotic events (composite of fatal or non-fatal myocardial infarction, ischemic stroke, acute limb ischemia/major amputation, systemic embolism, symptomatic venous thromboembolism), AV-access thrombosis, and clotting of the hemodialysis circuit. Of 308 participants randomized, 307 received study treatment and were analyzed. Fesomersen led to a dose-dependent and sustained reduction of steady-state median FXI levels by 53.6% (40 mg group), 71.3% (80 mg group), 86.0% (120 mg group), versus 1.9% in the placebo group. MB/CRNMB events occurred in 6.5% (40 mg group), 5.1% (80 mg group), 3.9% (120 mg group), and in 4.0% of those receiving placebo (pooled fesomersen placebo = 0.78). Major atherothrombotic events occurred in 1 patient (1.3%) in each treatment arm. MB/CRNMB bleeding and post-dialysis AV-access bleeding were not related to predicted FXI levels. Lower predicted FXI levels were associated with reductions in hemodialysis circuit clotting ( = 0.002) and AV-access thrombosis ( = 0.014). In patients with KF-HD, fesomersen produced a dose-dependent reduction in FXI levels associated with similar rates of major bleeding compared with placebo. URL: ; unique identifier:

中文翻译：

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一项 II 期随机对照试验评估了 fesomersen 对血液透析肾衰竭患者的抗血栓治疗

血液透析肾衰竭 (KF-HD) 患者发生动脉粥样硬化血栓事件和出血的风险很高。这项 IIb 期研究评估了 fesomersen（一种肝因子 XI 表达抑制剂）安慰剂对 KF-HD 患者出血和动脉粥样硬化血栓形成的剂量反应。患者被随机分配接受每月一次 40、80 或 120 mg fesomersen 或匹配的安慰剂，治疗时间长达 12 个月。主要安全性终点是大出血和临床相关非大出血（MB/CRNMB）的复合终点。探索性终点包括透析后动静脉（AV）通路出血、主要动脉粥样硬化血栓事件（致命或非致命性心肌梗死、缺血性中风、急性肢体缺血/大截肢、全身性栓塞、症状性静脉血栓栓塞）、AV-进入血栓形成和血液透析回路的凝血。在 308 名随机参与者中，307 人接受了研究治疗并进行了分析。 Fesomersen 导致稳态中位 FXI 水平呈剂量依赖性持续降低 53.6%（40 mg 组）、71.3%（80 mg 组）、86.0%（120 mg 组），而安慰剂组为 1.9%。在接受安慰剂的患者中，MB/CRNMB 事件的发生率为 6.5%（40 mg 组）、5.1%（80 mg 组）、3.9%（120 mg 组）和 4.0%（汇总 fesomersen 安慰剂 = 0.78）。每个治疗组有 1 名患者 (1.3%) 发生主要动脉粥样硬化血栓事件。 MB/CRNMB 出血和透析后 AV 通路出血与预测的 FXI 水平无关。较低的预测 FXI 水平与血液透析回路凝血 (= 0.002) 和 AV 通路血栓形成 (= 0.014) 的减少相关。在 KF-HD 患者中，与安慰剂相比，fesomersen 产生剂量依赖性的 FXI 水平降低，且大出血发生率相似。网址: ;唯一标识符：