Clinical trial NCT02610296: QPI-1002 for Prevention of Delayed Graft Function in Recipients of an Older Donor Kidney Transplant
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Delayed Graft Function
Lead sponsor: Quark Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-11-20
Enrollment: 594
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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).

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.

Eligibility criteria: 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).

Primary outcomes:
measure: The number of dialysis sessions through Day 30 for subjects who started dialysis beginning in the first 7 days post-transplant.
timeFrame: Day 0 to Day 30
Secondary outcomes:
measure: The proportion of subjects requiring dialysis for any reason in the first 7 days post-transplant.
timeFrame: Day 0 to Day 7
measure: The proportion of subjects with a decrease in serum creatinine of ≥ 10% on three consecutive days in the first 7 days post-transplant.
timeFrame: Day 0 to Day 7
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown Transplant Institute
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health, Shands Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: New York - Presbyterian Hospital / Weill Cornell Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate NY University Hospital
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Nazih Zuhdi Transplant Institute
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Baylor All Saints
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Universitario Austral
city: Buenos Aires
country: Argentina
facility: Instituto de Nefrología Trasplante Renal y Renopancreatico
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg
city: Liège 1
country: Belgium
facility: Centre Hospitalier - Universitaire de Liège
city: Fortaleza
country: Brazil
facility: Hospital Geral de Fortaleza
state: CE
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
state: PE
city: Rio de Janeiro
country: Brazil
facility: Hospital São Francisco de Assis
state: RJ
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: RS
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SP
city: São Paulo
country: Brazil
facility: Fundação Oswaldo Ramos - Hospital do Rim
state: SP
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
state: SP
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Praha 4
country: Czechia
facility: Klinika nefrologie IKEM
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Créteil
country: France
facility: Hospital Henri Mondor - Créteil
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Nice
country: France
facility: Hôpital Pasteur
city: Paris
country: France
facility: Hôpital Necker
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Rangueil
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK)
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Nieren und Hochdruckerkrankungen
city: Kiel
country: Germany
facility: University Hospital Schleswig Holstein, Campus Kiel
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Quark Pharmaceuticals
name: John Holman, M.D.,Ph.D.
role: STUDY_DIRECTOR
References: