TY - JOUR
T1 - YSPSL (rPSGL-Ig) for improvement of early renal allograft function
T2 - A double-blind, placebo-controlled, multi-center Phase IIa study
AU - Osama Gaber, A.
AU - Mulgaonkar, Shamkant
AU - Kahan, Barry D.
AU - Steve Woodle, E.
AU - Alloway, Rita
AU - Bajjoka, Iman
AU - Jensik, Stephen
AU - Klintmalm, Goran B.
AU - Patton, Pamela R.
AU - Wiseman, Alexander
AU - Lipshutz, Gerald
AU - Kupiec-Weglinski, Jerzy
AU - Gaber, Lilian W.
AU - Katz, Eliezer
AU - Irish, William
AU - Squiers, Elizabeth C.
AU - Hemmerich, Stefan
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/7
Y1 - 2011/7
N2 - Introduction: Recombinant P-selectin glycoprotein ligand IgG fusion protein, rPSGL-Ig (YSPSL), a fusion protein of human P-selectin ligand and IgG1-Fc, blocks leukocyte adhesion and protects against ischemia reperfusion injury (IRI) in animal models. Patients and Methods: This randomized 15-center, double-blind, 59-patient Ph2a study assessed YSPSL's safety in recipients of deceased-donor kidney allografts and its potential efficacy in improving early graft function. Two doses and two dosing modalities were evaluated. Results: No drug-specific toxicities or increased adverse event rates were noted. Two YSPSL-treated patients died of causes determined as unrelated to study drug. YSPSL did not reduce the incidence of dialysis within the first week post-transplant (41% in treated vs. 20% in placebo patients). Renal function endpoints scored at post-operative days 1 & 2 were also not impacted by YSPSL. However, at day 5, the fraction of patients with serum creatinine above 6mg/dL was lower in the YSPSL vs. placebo group (26% vs. 55%, p=0.043). Large variations in the dialysis-delayed graft function (DGF) rates were observed between centers, independently of treatment assignment, indicating subjectivity of this endpoint. Conclusion: In this first Ph2a study in kidney transplantation, YSPSL was safe but did not impact the dialysis-DGF rate. Further studies with more objective efficacy endpoints are required to define the impact of YSPSL on early renal allograft function.
AB - Introduction: Recombinant P-selectin glycoprotein ligand IgG fusion protein, rPSGL-Ig (YSPSL), a fusion protein of human P-selectin ligand and IgG1-Fc, blocks leukocyte adhesion and protects against ischemia reperfusion injury (IRI) in animal models. Patients and Methods: This randomized 15-center, double-blind, 59-patient Ph2a study assessed YSPSL's safety in recipients of deceased-donor kidney allografts and its potential efficacy in improving early graft function. Two doses and two dosing modalities were evaluated. Results: No drug-specific toxicities or increased adverse event rates were noted. Two YSPSL-treated patients died of causes determined as unrelated to study drug. YSPSL did not reduce the incidence of dialysis within the first week post-transplant (41% in treated vs. 20% in placebo patients). Renal function endpoints scored at post-operative days 1 & 2 were also not impacted by YSPSL. However, at day 5, the fraction of patients with serum creatinine above 6mg/dL was lower in the YSPSL vs. placebo group (26% vs. 55%, p=0.043). Large variations in the dialysis-delayed graft function (DGF) rates were observed between centers, independently of treatment assignment, indicating subjectivity of this endpoint. Conclusion: In this first Ph2a study in kidney transplantation, YSPSL was safe but did not impact the dialysis-DGF rate. Further studies with more objective efficacy endpoints are required to define the impact of YSPSL on early renal allograft function.
KW - Clinical trial
KW - Ischemia reperfusion injury
KW - Kidney transplant
KW - Selectins
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U2 - 10.1111/j.1399-0012.2010.01295.x
DO - 10.1111/j.1399-0012.2010.01295.x
M3 - Article
C2 - 20573162
AN - SCOPUS:80051689516
SN - 0902-0063
VL - 25
SP - 523
EP - 533
JO - Clinical Transplantation
JF - Clinical Transplantation
IS - 4
ER -