YSPSL (rPSGL‐Ig) for improvement of early renal allograft function: a double‐blind, placebo‐controlled, multi‐center Phase IIa study^1,2,3

Abstract

Gaber AO, Mulgaonkar S, Kahan BD, Woodle ES, Alloway R, Bajjoka I, Jensik S, Klintmalm GB, Patton PR, Wiseman A, Lipshutz G, Kupiec‐Weglinski J, Gaber LW, Katz E, Irish W, Squiers EC, Hemmerich S. YSPSL (rPSGL‐Ig) for improvement of early renal allograft function: A double‐blind, placebo‐controlled, multi‐center Phase IIa study. Clin Transplant 2011: 25: 523–533. © 2010 John Wiley & Sons A/S. 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.