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


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.


CONCLUSIONS
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.
Gaber
A Osama
AO
Methodist Hospital, Houston, TX, USA.
Mulgaonkar
Shamkant
S
Kahan
Barry D
BD
Woodle
E Steve
ES
Alloway
Rita
R
Bajjoka
Iman
I
Jensik
Stephen
S
Klintmalm
Goran B
GB
Patton
Pamela R
PR
Wiseman
Alexander
A
Lipshutz
Gerald
G
Kupiec-Weglinski
Jerzy
J
Gaber
Lilian W
LW
Katz
Eliezer
E
Irish
William
W
Squiers
Elizabeth C
EC
Hemmerich
Stefan
S
D000328:Adult; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000517:prevention & control; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D003404:Creatinine