A Study to Evaluate Efficacy and Safety of QPI-1002 for Prevention of Acute Kidney Injury Following Cardiac Surgery

Phase 2

Completed

Conditions: Acute Kidney Injury

Interventions: Drug: QPI-1002
Drug: Placebo

Registration Number: NCT02610283

Lead Sponsor: Quark Pharmaceuticals

Brief Summary: This trial is designed to evaluate QPI-1002 versus placebo for the prevention of AKI in subjects who are at high risk for AKI following cardiac surgery. Half of the participants will receive QPI-1002 while the other half will receive placebo.

Detailed Description: This is a randomized, double-blind, placebo-controlled, Phase 2 trial to evaluate QPI-1002 versus placebo for the prevention of AKI in subjects who are at high risk for AKI following cardiac surgery.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 341

Inclusion Criteria

Have the ability to understand the requirements of the study, are able to provide written informed consent and are willing and able to comply with the requirements of the study
Male or female, age ≥ 45 years old.
Have stable renal function per Investigator assessment and no known increase in serum creatinine of ≥ 0.3 mg/dL during preceding 4 weeks.
Scheduled to undergo non-emergent open chest cavity cardiovascular surgeries, including use of coronary pulmonary bypass (CPB) and no CPB:
- Combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve (valve(s) surgery) and at least 1 AKI Risk Factor;
- Surgery of more than one cardiac valve (valve surgery) and at least 1 AKI Risk Factor;
- Surgery of the aortic root or ascending part of the aorta, or in combination with the aortic valve, and at least 1 AKI Risk Factor; circulatory arrest is not excluded;
- Aortic root or ascending part of the aorta, combined with CABG and/or valve(s) surgery and at least 1 AKI Risk Factor; circulatory arrest is not excluded;
- If only CABG or single valve surgery, subjects are required to have at least 2 AKI Risk Factors:

AKI Risk Factors:

Age ≥ 70 years
eGFR ≤ 60 ml/min/1.73m2 by CKD-EPI formula at Screening.
Diabetes (Type 1 or 2), requiring at least 1 oral hypoglycemic agent or insulin
Proteinuria ≥ 0.3g/d, spot UPCR ≥ 0.3g/gm or urine dip stick ≥ +2
History of congestive heart failure requiring hospitalization

Exclusion Criteria

Have an eGFR ≤ 20 mL/min/1.73 m2
Subjects with an eGFR ≤ 60 mL/min/1.73 m2 requiring intravascular iodinated contrast within 48 hours of the day of surgery. However, subjects may be included if the post contrast increase in serum creatinine is < 0.3 mg/dl in at least 2 serum creatinine evaluations performed not less than 36 hours apart.
Have a history of any organ or cellular transplant which requires active immunosuppressive treatment which can interfere with kidney function
Emergent surgeries, including aortic dissection, and major congenital heart defects
Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR) or single vessel, mid-CAB off-pump surgeries or left ventricular assist device (LVAD) implantation
Have participated in an investigational drug study in the last 30 days
Have a known allergy to or had participated in a prior study with siRNA
Have a history of human immunodeficiency virus (HIV) infection
Have known active Hepatitis B (HBV) (Note: Subjects with a serological profile suggestive of clearance, or prior antiviral treatment of HBV infection may be enrolled)
Are HCV-positive (detectable HCV RNA) (Note: Subjects at least 24 weeks from completion of treatment with an antiviral regimen and who remain free of HCV as determined by HCV RNA testing may be enrolled.)
Have had cardiogenic shock or hemodynamic instability within the 24 hours prior to surgery, requiring inotropes or vasopressors or other mechanical devices such as intra-aortic balloon counter-pulsation (IABP)
Have required any of the following within a week prior to cardiac surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, left ventricular assist device (LVAD), other forms of mechanical circulatory support (MCS) (Note: The prophylactic insertion of an IABP preoperatively for reasons not related to existing LV pump function is not exclusionary).
Have required cardiopulmonary resuscitation within 14 days prior to cardiac surgery
Have ongoing sepsis or history of sepsis within the past 2 weeks or untreated diagnosed infection prior to Screening visit. Sepsis is defined as presence of a confirmed pathogen, along with fever or hypothermia, and hypoperfusion or hypotension
Have total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN) at time of screening
Have Child Pugh Class A liver disease with ALT/AST above the upper limit of normal or Class B or higher. (This criterion is only applicable in a patient population with underlying chronic liver disease, i.e., cirrhosis.)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QPI-1002	QPI-1002	QPI-1002 Injection, single dose
Placebo	Placebo	isotonic saline

Primary Outcome Measures

Name	Time	Method
Proportion of subjects developing AKI as defined by the AKIN criteria	Baseline through Day 5

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects developing at least on of the following events: death, needing renal replacement therapy (RRT) during the 90-day post-operative period, or having a ≥ 25% reduction in SCr based eGFR at the Day 90 visit	Baseline through Day 90

Trial Locations

Locations (36): Indiana Ohio Heart
🇺🇸
Fort Wayne, Indiana, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
St. John Regional Hospital
🇨🇦
Saint John, New Brunswick, Canada
Baylor University
🇺🇸
Dallas, Texas, United States
Jacksonville Center for Clinical Research
🇺🇸
Jacksonville, Florida, United States
Lindner Research Center, The Christ Hospital
🇺🇸
Cincinnati, Ohio, United States
Instiut Universitaire de Cardiologie et Pneumologie de Quebec
🇨🇦
Quebec City, Quebec, Canada
University of Florida
🇺🇸
Gainesville, Florida, United States
Washington University
🇺🇸
Saint Louis, Missouri, United States
Suburban Hospital
🇺🇸
Bethesda, Maryland, United States
Mid Michigan Cardiovascular Research
🇺🇸
Midland, Michigan, United States
Bryan Heart
🇺🇸
Lincoln, Nebraska, United States
Aurora St. Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Columbia University
🇺🇸
New York, New York, United States
Duke University
🇺🇸
Durham, North Carolina, United States
St. Michael's Hospital
🇨🇦
Toronto, Ontario, Canada
Montreal Heart Institute
🇨🇦
Montreal, Quebec, Canada
Herzzentrum Dresden GmbH
🇩🇪
Dresden, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪
Mainz, Germany
Herzzentrum Leipzig GmbH
🇩🇪
Leipzig, Germany
Westdeutsches Herzzentrum Essen / Universitätsklinikum Essen
🇩🇪
Essen, Germany
Klinikum der Universität zu Köln
🇩🇪
Köln, Germany
Universitätsklinikum Giessen und Marburg / Standort Giessen / Zentrum für Chirurgie
🇩🇪
Giessen, Germany
Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
Charité - Universitätsmedizin Berlin
🇩🇪
Berlin, Germany
River City Clinical Research
🇺🇸
Jacksonville, Florida, United States
University of Arizona Sarver Heart Center
🇺🇸
Tucson, Arizona, United States
Cardiac & Vascular Research Center of Northern Michigan
🇺🇸
Petoskey, Michigan, United States
St. Vincent Medical Group
🇺🇸
Indianapolis, Indiana, United States
Advocate Christ Medical Center
🇺🇸
Oak Lawn, Illinois, United States
University of Ottawa Heart Institute
🇨🇦
Ottawa, Ontario, Canada
Centre hospitalier de l'universite de Montreal
🇨🇦
Montreal, Quebec, Canada
Universitätsklinikum Heidelberg
🇩🇪
Heidelberg, Germany
Mcgill University Health Center - Royal Victoria Hospital
🇨🇦
Montreal, Quebec, Canada