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首页> 外文期刊>Allergy >Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate
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Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate

机译：皮下C1抑制剂浓缩液替代遗传性血管性水肿的II期研究结果

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Background: Hereditary angioedema (HAE) due to Cl inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long-term prophylaxis with twice-weekly intravenous injections of plasma-derived Cl-inhibitor (pdCl-INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdCl-INH has not been studied in patients with HAE. Methods: This open-label, dose-ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice-weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume-reduced CSL830 for 4 weeks each. The mean trough plasma levels of Cl-INH functional activity, Cl-INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model-derived steady-state trough Cl-INH functional activity. Results: After SC CSL830 administration, a dose-dependent increase in trough functional Cl-INH activity was observed. Cl-INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant Cl-INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdCl-INH SC injection with CSL830 showed a lower peak-to-trough ratio and more consistent exposures. All doses were well tolerated. Mild-to-moderate local site reactions were noted with pain and swelling being the most common adverse event. Conclusions: Subcutaneous volume-reduced CSL83O was well tolerated and led to a dose-dependent increase in physiologically relevant functional Cl-INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation.
机译：背景：由于缺乏Cl抑制剂而导致的遗传性血管性水肿（HAE）表现为反复发作的肿胀发作，可能致残甚至致命。已经建立了每周两次静脉注射血浆衍生的Cl抑制剂（pdCl-INH）的长期预防措施，作为一种有效的治疗方法。尚未对HAE患者的皮下（SC）施用pdCl-INH进行研究。方法：这项开放性，剂量范围，交叉研究（COMPACT II期）是针对18例I型或II型HAE患者进行的，他们接受了两次每周两次的1500、3000或6000 IU SC高度浓缩的剂量，每个CSL830减少4周。评估了第4周内Cl-INH功能活性，Cl-INH和C4抗原水平的平均谷值血浆水平以及总体安全性和耐受性。主要结果是模型来源的稳态谷Cl-INH功能活动。结果：SC CSL830给药后，观察到谷功能Cl-INH活性呈剂量依赖性增加。 Cl-INH和C4水平均增加。两个最高剂量组（3000和6000 IU）达到了恒定的Cl-INH活性水平，超过40％的值，该阈值被认为可为临床预防血管性水肿发作提供保护。与静脉注射相比，使用CSL830的pdCl-INH SC注射具有更低的峰谷比和更一致的暴露。所有剂量均耐受良好。注意到轻度至中度的局部反应，疼痛和肿胀是最常见的不良事件。结论：皮下体积减小的CSL83O具有良好的耐受性，并导致生理相关的功能性Cl-INH血浆水平呈剂量依赖性增加。 SC CSL830在HAE患者中的临床结果研究值得进一步研究。

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