NCT00802347

I5NP for Prophylaxis of Delayed Graft Function in Kidney Transplantation

Controlled, Randomized, Prospective, Double-Blind, Multicenter, Phase I/II, Dose-Escalation Study of the Safety, PK, and Clinical Activity of I5NP for Prophylaxis of Delayed Graft Function in Patients Undergoing Deceased Donor Kidney Transplantation

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 374 (actual)
• Sponsor: Quark Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether a single administration of QPI-1002 (also known as I5NP) can prevent DGF in patients undergoing deceased donor kidney transplantation. In this Phase I /II study, patients who are undergoing renal transplantation with organs from DCD donors, ECD donors or SCD donors with ≥ 24 hours of cold ischemia time who meet study entry criteria will be studied to evaluate the safety and pharmacokinetic profile of I5NP (Part A) and clinical activity of I5NP administration (Part B). Data from this study will be used to identify doses of I5NP to be used in follow-on efficacy studies. Part A will be a randomized, dose escalation study to determine the highest or maximum tolerated dose (MTD). Part A will enroll 40 patients at approximately 20 sites; patients will be randomized to receive either I5NP or placebo in a ratio of 8:2 in each cohort (cohorts 1-4). Part B will utilize the dose identified in Part A to further evaluate, in a double-blind manner, the safety, and clinical activity of I5NP. In Part B, up to 326 patients will participate at approximately 60 sites; up to 163 patients will be randomized to receive I5NP and up to 163 patients randomized to receive placebo.

Detailed description

Although the etiology of DGF is not fully understood and may be multifactorial, the pathophysiology appears to be primarily related to ischemia-reperfusion (IR) injury resulting from organ preservation between the times of harvesting from the donor and reperfusion following vascular reanastomosis in the recipient. I5NP is a small interfering RNA (siRNA) that is being developed for the prophylaxis of delayed graft function (DGF) in patients receiving renal transplants.

Conditions

• Delayed Graft Function
• Other Complication of Kidney Transplant

Interventions

Type	Name	Description
DRUG	I5NP	Single IV injection of I5NP Part A: dose-escalation study; cohort 1 = 0.5 mg/kg; cohort 2 = 1.5 mg/kg; cohort 3 = 5.0 mg/kg; cohort 4 = 10.0 mg/kg Part B: 10.0 mg/kg
DRUG	Saline	Single IV injection of saline Part A: dose-escalation study; cohort 1 = 0.5 mg/kg; cohort 2 = 1.5 mg/kg; cohort 3 = 5.0 mg/kg; cohort 4 = 10.0 mg/kg Part B: 10.0 mg/kg

Timeline

• Start date: 2008-12-01
• Primary completion: 2013-11-01
• Completion: 2014-05-01
• First posted: 2008-12-04
• Last updated: 2014-09-18

Locations

50 sites across 5 countries: United States, Canada, France, Germany, Spain