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

Clin Transplant. Jul-Aug 2011;25(4):523-33. doi: 10.1111/j.1399-0012.2010.01295.x. Epub 2010 Jun 22.

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 6 mg/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.

Trial registration: ClinicalTrials.gov NCT00298168 NCT00298181.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Creatinine / blood
  • Double-Blind Method
  • Female
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Recombinant Fusion Proteins / therapeutic use*
  • Reperfusion Injury / prevention & control
  • Tissue Donors
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Recombinant Fusion Proteins
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT00298168
  • ClinicalTrials.gov/NCT00298181