YSPSL for Prevention of Delayed Graft Function Part B

Kidney Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00298168
• Other study ID #: YSPSL-0001-PF Part B
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 27, 2006
• Last updated: January 24, 2008
• Start date: May 2006
• Est. completion date: December 2007

Study information

• Verified date: January 2008
• Source: Y's Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Delayed Graft Function
• Kidney Diseases

Intervention

Drug:
• YSPSL
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
• placebo
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
• YSPSL
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

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati, Department of Internal Medicine	Cincinnati	Ohio
United States	Baylor University Medical Center Transplantation Services	Dallas	Texas
United States	University of Colorado Health Sciences Center	Denver	Colorado
United States	Henry Ford Hospital Transplant Institute	Detroit	Michigan
United States	Shands Hospital at University of Florida	Gainesville	Florida
United States	Westchester Medical Center, New York Medical College	Hawthorne	New York
United States	The Methodist Hospital	Houston	Texas
United States	University of Texas, Organ Transplantation	Houston	Texas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Dumont-UCLA Transplant Center	Los Angeles	California
United States	Methodist Healthcare University Hospital	Memphis	Tennessee
United States	Tulane University Hospital & Clinic	New Orleans	Louisiana
United States	California Pacific Medical Center Department of Transplantation	San Francisco	California
United States	Lifelink Foundation	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Y's Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	delayed graft function post transplant		6 months	Yes
Secondary	renal function parameters through 6 months post transplant		6 months