YSPSL (rPSGL-Ig) for improvement of early renal allograft function: A double-blind, placebo-controlled, multi-center Phase IIa study

A. Osama Gaber, Shamkant Mulgaonkar, Barry D. Kahan, E. Steve Woodle, Rita Alloway, Iman Bajjoka, Stephen Jensik, Goran B. Klintmalm, Pamela R. Patton, Alexander Wiseman, Gerald Lipshutz, Jerzy Kupiec-Weglinski, Lilian W. Gaber, Eliezer Katz, William Irish, Elizabeth C. Squiers, Stefan Hemmerich

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)523-533
Number of pages11
JournalClinical Transplantation
Volume25
Issue number4
DOIs
StatePublished - Jul 2011

Keywords

  • Clinical trial
  • Ischemia reperfusion injury
  • Kidney transplant
  • Selectins

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'YSPSL (rPSGL-Ig) for improvement of early renal allograft function: A double-blind, placebo-controlled, multi-center Phase IIa study'. Together they form a unique fingerprint.

Cite this