Clinical Trial: I5NP for Prophylaxis of Delayed Graft Function in Kidney Transplantation
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: 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 Graf
Brief 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 Summary:
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.
Sponsor: Quark Pharmaceuticals
Current Primary Outcome: Part A: The outcome measure is safety. Additionally, plasma blood levels will be measured to characterize the PK of I5NP in this patient population. Part B: The outcome measure will be safety and the incidence of delayed graft function. [ Time Frame: Part A: DSMB review at conclusion of each cohort / Part B: Interim analyses will be performed after the 66th, 130th, and 196th patient enrolled ]
Original Primary Outcome: Number of Dose Limiting Toxicities (DLTs) observed among 4 cohorts of 10 patients per cohort [ Time Frame: Reviewed at the conclusion of each cohort ]
Current Secondary Outcome: Part B: Treatment differences in the rate of improvement in renal function over time and treatment differences in the need for renal replacement therapy. [ Time Frame: Part B: Interim analyses will be performed after the 66th, 130th, and 196th patient enrolled ]
Original Secondary Outcome:
Information By: Quark Pharmaceuticals
Dates:
Date Received: December 2, 2008
Date Started: December 2008
Date Completion:
Last Updated: September 8, 2014
Last Verified: September 2014
