A phase Ib, open-label, single arm study to assess the safety, pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end-stage renal disease
A phase Ib, open-label, single arm study to assess the safety, pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end-stage renal disease
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DOI：
10.1111/ctr.13155
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发表时间：
2018-01-01
影响因子：
2.1
通讯作者：
Alloway, Rita R.
中科院分区：
文献类型：
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作者：
Abu Jawdeh, Bassam G.;Woodle, Ervin Steve;Alloway, Rita R.
在肾移植中研究脱敏的奋进还没有与研究预防致敏的策略的努力相匹配。在本研究（NCT 02437422）中，我们研究了SANGUINATE（SG）（一种基于血红蛋白的氧载体）作为浓缩红细胞（PRBC）的潜在替代品在终末期肾病（ESRD）移植候选人中的安全性、对致敏性的影响和药代动力学。10例符合入选/排除（I/E）标准的ESRD受试者计划接受每周3次SG输注（320 mg/kg）。入组5例受试者后停止研究，并在完成90天随访期后分析其数据。2例受试者在SG输注时肌钙蛋白I水平升高，其中1例被解释为非ST段抬高型心肌梗死。所有其他不良事件均为一过性。SG药代动力学分析显示平均（SD）C-max、T-max、AUC和半衰期分别为4.39（0.69）mg/mL、2.42（0.91）小时、171.86（52.35）mgh/mL和40.60（11.96）小时。SG输注后和整个研究期间，无受试者产生新的抗HLA抗体。总之，SG是考虑进行肾移植的ESRD患者中PRBC的潜在替代品，因为它与体液致敏无关。需要在高致敏患者中进行更大规模的研究，以进一步评价潜在的安全性信号。
The endeavor to study desensitization in kidney transplantation has not been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization, and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive three weekly infusions of SG (320mg/kg). The study was stopped after five subjects were enrolled, and their data were analyzed after completing a follow-up period of 90days. Two subjects had elevated troponin I levels in setting of SG infusion, one of which was interpreted as a non-ST elevation myocardial infarction. All other adverse events were transient. SG pharmacokinetic analysis showed mean (SD) C-max, T-max, AUC, and half-life of 4.39 (0.69) mg/mL, 2.42 (0.91) hours, 171.86 (52.35) mgh/mL, and 40.60 (11.96) hours, respectively. None of the subjects developed new anti-HLA antibodies following SG infusion and throughout the study period. In conclusion, SG is a potential alternative to PRBCs in ESRD patients considered for kidney transplantation as it was not associated with humoral sensitization. Larger studies in highly sensitized patients are required to further evaluate for potential safety signals.