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

The endeavor to study desensitization in kidney transplantation hasn't 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 3 weekly infusions of SG (320mg/Kg). The study was stopped after 5 subjects were enrolled and their data was analyzed after completing a follow up period of 90 days. 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) Cmax, Tmax, AUC and half-life of 4.39(0.69)mg/ml, 2.42(0.91)hours, 171.86(52.35)mg.hour/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. This article is protected by copyright. All rights reserved.