I5NP for Prophylaxis of Delayed Graft Function in Kidney Transplantation

NCT00802347 | Completed Phase 1 DMC

• 1 other identifier: QRK.006
• Study Type: interventional
• Target: 374
• Locations: 5 countries
• Sites: 50

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.

Conditions

Delayed Graft Function; Other Complication of Kidney Transplant

Keywords

Delayed Graft Function; Kidney Transplant; Renal Transplant; small interfering ribonucleic acid (siRNA)

Outcome Measures

Primary Outcomes (1)

• 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.

  Part A: DSMB review at conclusion of each cohort / Part B: Interim analyses will be performed after the 66th, 130th, and 196th patient enrolled

Secondary Outcomes (1)

• Part B: Treatment differences in the rate of improvement in renal function over time and treatment differences in the need for renal replacement therapy.

  Part B: Interim analyses will be performed after the 66th, 130th, and 196th patient enrolled

Study Arms (2)

I5NP

EXPERIMENTAL

Drug: I5NP

Saline

PLACEBO COMPARATOR

Drug: Saline

Interventions

I5NP DRUG

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

Also known as: QPI-1002

I5NP

Saline DRUG

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

Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is at least 18 years of age.
• Patient has given informed consent.
• 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 or using 2 methods of birth control concurrently, whichever is more stringent) 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 or using 2 methods of birth control concurrently, whichever is more stringent) 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 consistent with ESRD. 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.
• Women of childbearing potential test negative for pregnancy (either urine or serum) within 48 hours prior to transplant.
• Patient is up-to-date on cancer screening according to site-specific guidelines and the past medical history is negative for biopsy-confirmed malignancy within 5 years of randomization, with the exception of adequately treated basal cell or squamous cell carcinoma in situ.
• Patient is scheduled to receive kidney transplant from a deceased donor meeting the following criteria:
• Part A:
• receipt of an extended criteria donor (ECD) kidney, or
• receipt of a kidney donated after cardiac death (DCD), or
• receipt of a standard criteria donor (SCD) with cold ischemia time (CIT) ≥ 24 hours.
• Part B:
• receipt of an ECD kidney that has been preserved by cold storage (ECD/CS) for the entire period of cold ischemia time (CIT), regardless of duration
• receipt of an ECD kidney that has been preserved by machine perfusion (ECD/MP) for any interval of time during the period of cold ischemia, where total CIT has been at least 26 hours
• receipt of an SCD kidney that has been preserved by cold storage (SCD/CS) where total CIT has been at least 26 hours
• receipt of an SCD kidney that has been preserved by machine perfusion (SCD/MP) for any interval of time during the period of cold ischemia, where total CIT has been at least 26 hours.

You may not qualify if:

• Patient has participated in an investigational drug study in the last 30 days.
• Patient has known allergy or has participated in prior study with siRNA.
• Patient is HCV-positive
• Patient is HIV-positive
• Patient is scheduled to undergo multiorgan transplantation.
• Patient has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant).
• Patient has planned transplant of kidneys from donors \< 6 years of age.
• Patient has planned transplant of dual kidneys (from the same donor) transplanted not en bloc (as in the case of dual ECD donor kidneys).
• 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.
• Patient is scheduled to receive a living donor kidney.
• Patient is scheduled to receive an ABO-incompatible donor kidney.
• Patient is scheduled to receive an organ from a donor that meets both DCD and ECD criteria.
• 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.

Sponsors & Collaborators

• Quark Pharmaceuticals: lead

Study Sites (50)

University of Alabama Birmingham

Birmingham, Alabama, 35294, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Transplant Research Institute (TRI; formerly NIT)

Los Angeles, California, 90057, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

University of Colorado Health Science Center

Aurora, Colorado, 80045, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Lifelink Healthcare Institute

Tampa, Florida, 33606, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

University of Illinois Chicago

Chicago, Illinois, 60612, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cornell University

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Wake Forest University Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Baylor All Saints Medical Center

Fort Worth, Texas, 76104, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University (MCV)

Richmond, Virginia, 23298, United States

Location

St. Paul's Hospital, Univeristy of BC

Vancouver, British Columbia, Canada

Location

UBC - Division of Nephrology

Vancouver, British Columbia, Canada

Location

QE II Capital District Health Authority, Halifax

Halifax, Nova Scotia, Canada

Location

MUHC Royal Victoria Hospital

Montreal, Quebec, Canada

Location

Hôpital Pasteur

Nice, France

Location

Hôpital Necker

Paris, France

Location

CHU Rangueil

Toulouse, France

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Charité, Campus Virchow-Klinikum

Berlin, Germany

Location

Kliniken der Stadt Köln gGmbH

Cologne, Germany

Location

Universitätklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Hospital de bellvitge

Barcelona, Spain

Location

Hospital del mar

Barcelona, Spain

Location

Hospital Vall Hebron

Barcelona, Spain

Location

MeSH Terms

Conditions

Delayed Graft Function

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Shai Erlich, Ph.D.

  Quark Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2008
• First Posted: December 4, 2008
• Study Start: December 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: May 1, 2014
• Last Updated: September 18, 2014

Record last verified: 2014-09

Locations

FR (3); US (33); DE (7); ES (3); CA (4)