YSPSL for Prevention of Delayed Graft Function Part B

Study Overview
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Brief Summary
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Selectins have been implicated in the pathogenesis of ischemia/reperfusion (I/R)-induced kidney injury and resultant delayed graft function (DGF). PSGL-1 is a ligand for P-, E-, and L-selectin. It has been reported that YSPSL (rPSGL-Ig) blocks P-selectin and, to a lesser degree, E- and L-selectin. Both sPSGL-1 and YSPSL (rPSGL-Ig) have been shown in animal models to reduce both cytokines and tissue damage associated with ischemia reperfusion and to improve renal function post-transplant. Therefore, the current phase I/II clinical study is designed to assess the safety and efficacy of YSPSL (rPSGL-Ig) in preventing DGF in patients undergoing cadaveric kidney transplants and to determine a dose for future pivotal studies.

Detailed Description
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This will be a multicenter, single-dose, dose-escalation study. The study will be in 2 parts: the first, Part A, will be an open label evaluation of single doses of four dose cohorts; the second, Part B will be a randomized, double-blind, placebo-controlled, single-dose study of two dose cohorts. Patients who are undergoing cadaveric kidney transplantation and are at risk for development of DGF, based upon known risk factors, will be eligible to participate in the study. A maximum of 24 patients will be enrolled in Part A. 60 patients will be enrolled in Part B.

Official Title
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Controlled, Randomized, Prospective, Double-Blind, Multicenter, Phase I/II, Dose-Escalation Study of the Safety, PK, and Efficacy of YSPSL for Prevention of Delayed Graft Function in Patients Undergoing Cadaveric Kidney Transplantation

Conditions
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Kidney Diseases

Intervention / Treatment
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* Drug: YSPSL
* Drug: placebo
* Drug: YSPSL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing primary cadaver renal transplants Exclusion Criteria: Patient has a planned transplant of a donor kidney from a non-heart beating donor Patient has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant) or from donors < 6 years of age Patient has a planned transplant of a kidney from a donor who has received investigational therapies designed to reduce the impact of ischemia/reperfusion (I/R) injury, DGF, or other donor-related immune events Patient is planned to receive a living donor kidney; or patient is planned to receive an ABO-incompatible donor kidney

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: YSPSL<br>* YSPSL administered intravenously (IV) as a single bolus infusion of 1 mg/kg with 200 mL Lactated Ringer's for Injection USP total volume administered as an ex vivo flush intra-arterially to donor organ prior to implantation<br>* Other names: recombinant P-selectin glycoprotein ligand-Ig;|
| Experimental: 2<br> | Drug: YSPSL<br>* YSPSL administered intravenously (IV) as a single bolus infusion of 1 mg/kg with 10 mg YSPSL in 200 mL Lactated Ringer's for Injection USP total volume administered as an ex vivo flush intra-arterially to donor organ prior to implantation<br>* Other names: recombinant P-selectin glycoprotein ligand-Ig;|
| Placebo Comparator: 3<br> | Drug: placebo<br>* 0.9% normal saline administered IV as a single bolus infusion with 200 mL Lactated Ringer's for Injection USP total volume administered as an ex vivo flush intra-arterially to donor organ prior to implantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| delayed graft function post transplant |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| renal function parameters through 6 months post transplant |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delayed Graft Function