Henry Ford Hospital, Detroit, MI, USA.
BMC Nephrol. 2012 Aug 30;13:95. doi: 10.1186/1471-2369-13-95.
Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently.
Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa-to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within ±1.0 g/dL from baseline.
A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was ≤29 weeks. Overall, the proportion of patients with hemoglobin levels within ±1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2-13) to 54% (Weeks 18-25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents.
The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.
ClinicalTrials.gov registration: NCT00228449.
培利塞肽是一种基于肽的红细胞生成刺激剂，专门设计和制造用于刺激红细胞生成所必需的促红细胞生成素受体二聚体。这项 2 期剂量发现研究的主要目的是确定每月一次的培利塞肽给药方案，即在从促红细胞生成素α转换后，将血红蛋白维持在基线值 ±1.0g/dL 以内；同时评估培利塞肽的安全性。
接受稳定促红细胞生成素α治疗方案的慢性血液透析患者，按不同方案（1）确定培利塞肽起始剂量（使用单一促红细胞生成素α至培利塞肽剂量转换比或分层、基于体重或绝对剂量转换表），以及（2）是否使用 1 周无促红细胞生成素刺激剂间隔，依次分组。培利塞肽剂量滴定以维持血红蛋白水平从基线值 ±1.0g/dL。
共纳入 164 例患者，接受静脉内培利塞肽每 4 周 1 次，最多 6 个剂量；包括随访在内的研究持续时间≤29 周。总的来说，从研究开始到研究结束，血红蛋白水平在基线值 ±1.0g/dL 内的患者比例从 39%（第 2-13 周）增加到 54%（第 18-25 周）。使用分层剂量转换表的队列倾向于比使用单一剂量转换比的队列具有更稳定的培利塞肽剂量。此外，使用无促红细胞生成素刺激剂间隔的队列与不使用这种间隔的队列相比，血红蛋白水平没有出现显著的初始升高。在这项研究中，培利塞肽的安全性与已上市的促红细胞生成素刺激剂一致。
这项研究的结果用于指导随后进行的 3 期研究中的给药方案。每月一次的培利塞肽在血液透析患者中是可行的。
ClinicalTrials.gov 注册号：NCT00228449。
