Clinical trial NCT00298168: YSPSL for Prevention of Delayed Graft Function Part B
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Kidney Diseases
Keywords: Delayed Graft Function
Lead sponsor: Y's Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2006-03-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: delayed graft function post transplant
timeFrame: 6 months
Secondary outcomes:
measure: renal function parameters through 6 months post transplant
timeFrame: 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Dumont-UCLA Transplant Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Department of Transplantation
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Gainesville
country: United States
facility: Shands Hospital at University of Florida
state: Florida
city: Tampa
country: United States
facility: Lifelink Foundation
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Hospital & Clinic
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Hospital Transplant Institute
state: Michigan
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Hawthorne
country: United States
facility: Westchester Medical Center, New York Medical College
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati, Department of Internal Medicine
state: Ohio
city: Memphis
country: United States
facility: Methodist Healthcare University Hospital
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center Transplantation Services
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas, Organ Transplantation
state: Texas
Study officials:
affiliation: Y's Therapeutics, Inc.
name: Stefan Hemmerich, PhD
role: STUDY_DIRECTOR
References:
citation: Cheadle C, Watkins T, Ehrlich E, Barnes K, Gaber AO, Hemmerich S, Rabb H. Effects of anti-adhesive therapy on kidney biomarkers of ischemia reperfusion injury in human deceased donor kidney allografts. Clin Transplant. 2011 Sep-Oct;25(5):766-75. doi: 10.1111/j.1399-0012.2010.01365.x. Epub 2010 Nov 28.
citation: 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 Jul-Aug;25(4):523-33. doi: 10.1111/j.1399-0012.2010.01295.x. Epub 2010 Jun 22.