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I5NP for Prophylaxis of Delayed Graft Function in Kidney Transplantation
This study is ongoing, but not recruiting participants.
First Received: December 2, 2008   Last Updated: January 4, 2010   History of Changes
Sponsor: Quark Pharmaceuticals
Information provided by: Quark Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00802347
  Purpose

The purpose of this study is to determine whether a single administration of 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, approximately 200 patients will participate at approximately 40 sites; 100 patients will be randomized to receive I5NP and 100 patients randomized to receive placebo.


Condition Intervention Phase
Delayed Graft Function
Kidney Transplant
Drug: I5NP
Drug: Saline
Phase I
Phase II

Study Type: Interventional
Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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 Graft Function in Patients Undergoing Deceased Donor Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by Quark Pharmaceuticals:

Primary Outcome Measures:
  • 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 approximately one-third and then two-thirds of patients have been enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part B: Treatment differences in the rate of improvement in renal function over time [ Time Frame: Part B: Interim analyses will be performed after approximately one-third and then two-thirds of patients have been enrolled ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: December 2008
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
I5NP: Experimental 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: highest or maximum tolerated dose from Part A (up to 10.0 mg/kg)

Saline: Placebo Comparator 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: up to 10.0 mg/kg


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient is at least 18 years of age.
  2. Patient has given informed consent.
  3. Patient is willing to practice birth control. Female patients must be: (1) post-menopausal (2) surgically sterile, or (3) using an effective means of contraception (per the site-specific guidelines) which will be continued until the Study Day 90 visit with a negative pregnancy test within 48 hours prior to administration of study drug. Male patients with female partners of child bearing potential must agree to use an effective means of contraception (per the site-specific guidelines) which will be continued until the Study Day 90 visit. Note: For the purpose of this study, post menopausal is defined as the absence of menses for at least one year and a serum FSH level ≥ 20 IU/L. Investigators can determine if a serum FSH level is required to prove post-menopausal status. A woman is considered to be surgically sterilized if she has had a bilateral tubal ligation for at least 6 months prior to administration of study drug, bilateral oophorectomy, or complete hysterectomy.
  4. Women of childbearing potential test negative for pregnancy (either urine or serum) within 48 hours prior to transplant.
  5. Patient is up-to-date on cancer screening according to site-specific guideline.
  6. Patient is scheduled to receive kidney transplant from a deceased donor meeting the criteria for an ECD, DCD, or a SCD with cold ischemia time (CIT) ≥ 24 hours
  7. Patient is dialysis dependent at the time of transplant as documented by: a) the requirement for at least 2 dialysis sessions/week during the 56 days prior to transplant, or b) the planned removal of any remaining native kidney at the time of transplant, or c) the opinion of the investigator that the patient has no remaining native renal function.

Exclusion Criteria:

  1. Patient has participated in an investigational drug study in the last 30 days.
  2. Patient has known allergy or has participated in prior study with siRNA.
  3. Patient is HCV-positive
  4. Patient is HIV-positive
  5. Patient is scheduled to undergo multiorgan transplantation.
  6. Patient has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant).
  7. Patient has planned transplant of kidneys from donors < 6 years of age.
  8. Patient has planned transplant of dual kidneys (from the same donor) transplanted not en bloc (as in the case of dual ECD donor kidneys).
  9. Patient is scheduled for transplantation of a kidney from a donor who is known to have received an investigational therapy (under another IND) for ischemic/reperfusion injury immediately prior to organ recovery.
  10. Patient is scheduled to receive a living donor kidney.
  11. Patient is scheduled to receive an ABO-incompatible donor kidney.
  12. Patient is scheduled to receive an organ from a donor that meets both DCD and ECD criteria.
  13. Patient has history or presence of a medical condition or disease that in the investigator's assessment would place the patient at an unacceptable risk for study participation.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00802347

Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
UCSF Medical Center
San Francisco, California, United States, 94143
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Colorado
University of Colorado Health Science Center
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Lifelink Healthcare Institute
Tampa, Florida, United States, 33606
United States, Illinois
University of Illinois Chicago
Chicago, Illinois, United States, 60612
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New Jersey
Saint Barnabas Medical Center
Livingston, New Jersey, United States, 07039
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
Wake Forest University Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
The Christ Hospital
Cincinnati, Ohio, United States, 45219
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Baylor All Saints Medical Center
Fort Worth, Texas, United States, 76104
The Methodist Hospital
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Quark Pharmaceuticals
Investigators
Study Director: Martin S. Polinsky, MD Quark Pharmaceuticals
  More Information

No publications provided

Responsible Party: Quark Pharmaceuticals, Inc. ( Mike Johnston, Director of Regulatory Affairs )
Study ID Numbers: QRK.006
Study First Received: December 2, 2008
Last Updated: January 4, 2010
ClinicalTrials.gov Identifier: NCT00802347     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Quark Pharmaceuticals:
Delayed Graft Function
Kidney Transplant
Renal Transplant
small interfering ribonucleic acid (siRNA)

Additional relevant MeSH terms:
Pathologic Processes
Delayed Graft Function

ClinicalTrials.gov processed this record on February 08, 2010