QPI-1002 for Prevention of Delayed Graft Function in Recipients of an Older Donor Kidney Transplant (ReGIFT)

A Phase 3, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of QPI-1002 for Prevention of Delayed Graft Function in Recipients of a Donation After Brain Death Older Donor Kidney Transplant

The purpose of this trial is to evaluate the reduction in incidence and severity of delayed graft function with kidney allografts from donors >45 years after brain death (DBD).

Study Overview

• Status: Completed
• Conditions: Delayed Graft Function
• Intervention / Treatment: Drug: QPI-1002; Other: Placebo

Detailed Description

This is a Phase 3 randomized, placebo-controlled, double-blind, multi-center trial stratified by donor age and by region to evaluate the reduction in incidence and severity of delayed graft function with kidney allografts from DBD donors who were at least 45 years of age.

• Study Type: Interventional
• Enrollment (Actual): 594
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1500
    • Hospital Universitario Austral
  • Buenos Aires, Argentina, 3889
    • Instituto de Nefrología Trasplante Renal y Renopancreatico
• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven - Campus Gasthuisberg
  • Liège 1, Belgium, 4000
    • Centre Hospitalier - Universitaire de Liège
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60156-290
      • Hospital Geral de Fortaleza
  • PE
    • Recife, PE, Brazil, 50070-550
      • Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20530-001
      • Hospital São Francisco de Assis
  • RS
    • Porto Alegre, RS, Brazil, 90035-074
      • Santa Casa de Misericordia de Porto Alegre
  • SP
    • São José do Rio Preto, SP, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
    • São Paulo, SP, Brazil, 04038-002
      • Fundação Oswaldo Ramos - Hospital do Rim
    • São Paulo, SP, Brazil, 05403-900
      • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• Czechia
  • Praha 4, Czechia, 140 24
    • Klinika nefrologie IKEM
• France
  • Bordeaux, France, 33076
    • Hôpital Pellegrin
  • Créteil, France, 94010
    • Hospital Henri Mondor - Créteil
  • La Tronche, France, 38700
    • Centre Hospitalier Universitaire de Grenoble
  • Lyon, France, 69437
    • Hôpital Edouard Herriot
  • Nice, France, 06001
    • Hopital Pasteur
  • Paris, France, 75015
    • Hopital Necker
  • Toulouse, France, 31059
    • Centre Hospitalier Universitaire de Rangueil
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 13353
    • Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK)
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover, Klinik für Nieren und Hochdruckerkrankungen
  • Kiel, Germany, 24105
    • University Hospital Schleswig Holstein, Campus Kiel
  • Tübingen, Germany, D-72076
    • Universitätsklinikum Tübingen
• Netherlands
  • Groningen, Netherlands, 9713
    • University Medical Center Groningen
  • Leiden, Netherlands, 2333
    • Leids Universitair Medisch Centrum
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Centre
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d´Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Valencia, Spain, 46600
    • Hospital Universitario Doctor Peset
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias I Pujol
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Phoenix
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles
    • Sacramento, California, United States, 95817
      • University of California, Davis
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Transplant Institute
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Health, Shands Hospital
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • University of Maryland
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • St. Barnabas Medical Center
  • New York
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mt. Sinai
    • New York, New York, United States, 10065
      • New York - Presbyterian Hospital / Weill Cornell Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate NY University Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Nazih Zuhdi Transplant Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Fort Worth, Texas, United States, 76104
      • Baylor All Saints
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has the ability to understand the requirements of the study, is able to provide written informed consent and is willing and able to comply with the requirements of the study protocol.
• Male or female at least 18 years of age.
• Has dialysis dependent renal failure initiated at least 2 months prior to transplantation.
• Is to be a recipient of a transplant from a deceased donor (brain death criteria) ≥ 45 years of age.

• Based on donor age, the following requirements for the risk of DGF (determined using the Irish DGF risk assessment nomogram) and cold ischemia time (CIT) must be met:

  • Donor age 45 - 59 years: estimated DGF risk ≥ 20% and estimated CIT ≥ 10 hour
  • Donor age ≥ 60 years: no minimum estimated DGF risk or minimum estimated CIT
• Is able to comply with the requirement of antibody induction therapy with rabbit polyclonal anti-thymocyte globulin or anti-CD25 (anti-IL2R) monoclonal antibodies per center standard of care.
• Must be up-to-date on cancer screening according to site-specific guidelines and past medical history must be negative for biopsy-confirmed malignancy within 5 years of randomization, with the exception of adequately treated basal cell or squamous cell carcinoma in situ or carcinoma of the cervix in situ.

Exclusion Criteria:

• Recipient of a live donor kidney or a kidney from a donation after cardiac death (DCD) donor.
• Recipient of donor kidney preserved with normothermic machine perfusion.
• Scheduled to undergo multiorgan transplantation.
• Has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant).
• Has planned transplant of dual kidneys (from the same donor) transplanted not en bloc.
• Has lost first kidney transplant due to graft thrombosis.
• Is scheduled for transplantation of a kidney from a donor who is known to have received an investigational therapy under another IND/CTA for ischemic/reperfusion injury immediately prior to organ recovery.
• Is scheduled to receive an ABO-incompatible donor kidney.
• Has a positive T- or B-cell cross-match by NIH anti-globulin lymphocytotoxicity method or CDC crossmatch method, if performed.
• Has a positive T- or B-cell flow cross-match AND donor specific anti-HLA antibody (DSA) detected by flow cytometry, Luminex® based antigen-specific anti-HLA antibody testing, or by similar methodology, if performed.
• Has undergone desensitization to remove donor specific anti-HLA antibodies prior to transplantation.
• Has participated in an investigational study within the last 30 days or received an investigational product within 5 half-lives of the study drug administration, whichever is longest.
• Has known allergy to or has participated in a prior study with siRNA.
• Has a history of HBV (Note: subjects with a serological profile suggestive of clearance, or prior antiviral treatment of a prior HBV infection, may be enrolled with the approval of the Medical Monitor).
• Has a history of HIV.
• Recipient of a known HIV positive donor kidney.
• Is HCV-positive (detectable HCV RNA) (Note: Subjects at least 24 weeks from completion of treatment with an approved antiviral regimen and who remain free of HCV as determined by HCV RNA testing may be enrolled. Subjects who have been cleared of HCV virus after treatment with an unapproved regimen should be approved by the Medical Monitor).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; isotonic saline	Other: Placebo; isotonic saline
Active Comparator: QPI-1002; QPI-1002 Injection, single dose	Drug: QPI-1002; IV injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of dialysis sessions through Day 30 for subjects who started dialysis beginning in the first 7 days post-transplant.	Day 0 to Day 30

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of subjects requiring dialysis for any reason in the first 7 days post-transplant.	Day 0 to Day 7
The proportion of subjects with a decrease in serum creatinine of ≥ 10% on three consecutive days in the first 7 days post-transplant.	Day 0 to Day 7

Collaborators and Investigators

• Sponsor: Quark Pharmaceuticals
• Investigators: Study Director: John Holman, M.D.,Ph.D., Quark Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): June 28, 2018
• Study Completion (Actual): January 8, 2019

Study Registration Dates

• First Submitted: November 18, 2015
• First Submitted That Met QC Criteria: November 19, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Actual): May 13, 2020
• Last Update Submitted That Met QC Criteria: May 7, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Delayed Graft Function
• Other Study ID Numbers: QRK306