rPSGLaIg for Improvement of Early Liver Allograft Function: A DoubleaBlind, PlaceboaControlled, SingleaCenter Phase II StudyaNB

• Published in: American journal of transplantation Vol. 11; no. 4; pp. 786 - 797
• Main Authors: Busuttil, R W, Lipshutz, G S, KupiecaWeglinski, J W, Ponthieux, S, Gjertson, D W, Cheadle, C, Watkins, T, Ehrlich, E, Katz, E, Squiers, E C, Rabb, H, Hemmerich, S
• Format: Journal Article
• Language: English
• Published: 01.04.2011
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2011.03441.x

The selectin antagonist known as recombinant P-selectin glycoprotein ligand IgG (rPSGL-Ig) blocks leukocyte adhesion and protects against transplantation ischemia reperfusion injury (IRI) in animal models. This randomized (1:1) single-center double-blind 47-patient phase 2 study with 6-month follow-up assessed rPSGL-Ig's safety and impact on early graft function at 1 mg/kg systemic dose with pretransplant allograft ex vivo treatment in deceased-donor liver transplant recipients. Safety was assessed in all patients, whereas efficacy was assessed in a prospectively defined per-protocol patient set (PP) by peak serum transaminase (TA) and bilirubin values, and normalization thereof. In PP patients, the incidence of poor early graft function (defined as peak TA >2500 U/L or bilirubin >10 mg/dL), average peak liver enzymes and bilirubin, normalization thereof and duration of primary and total hospitalization trended consistently lower in the rPSGL-Ig group compared to placebo. In patients with donor risk index above study-average, normalization of aspartate aminotransferase was significantly improved in the rPSGL-Ig group (p < 0.03). rPSGL-Ig treatment blunted postreperfusion induction versus placebo of IRI biomarker IP-10 (p < 0.1) and augmented cytoprotective IL-10 (p < 0.05). This is the first clinical trial of an adhesion molecule antagonist to demonstrate a beneficial effect on liver transplantation IRI and supported by therapeutic modulation of two hepatic IRI biomarkers. Treatment with rPSGL-Ig, a P-selectin antagonist, improved early liver allograft function in a double-blinded, placebo-controlled, single-center Phase II study, in association with decreased IP-10 and augmented IL-10 expression.