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

A Randomized, Double-Blind, Placebo Controlled , Phase 2 Study to Evaluate the Efficacy and Safety of QPI-1002 for the Prevention of Acute Kidney Injury in Subjects at High Risk for AKI Following Cardiac Surgery

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.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Placebo; Drug: QPI-1002

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.

• Study Type: Interventional
• Enrollment (Actual): 341
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • St. John Regional Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences
    • Ottawa, Ontario, Canada, K1Z4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center - Royal Victoria Hospital
    • Montreal, Quebec, Canada, J0N 1P0
      • Montreal Heart Institute
    • Quebec City, Quebec, Canada, G1V4G5
      • Instiut Universitaire de Cardiologie et Pneumologie de Quebec
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Dresden, Germany, 01307
    • Herzzentrum Dresden GmbH
  • Essen, Germany, 45122
    • Westdeutsches Herzzentrum Essen / Universitätsklinikum Essen
  • Giessen, Germany, 35385
    • Universitätsklinikum Giessen und Marburg / Standort Giessen / Zentrum für Chirurgie
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Köln, Germany, 50937
    • Klinikum der Universität zu Köln
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig GmbH
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Sarver Heart Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32216
      • River City Clinical Research
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Indiana Ohio Heart
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
    • Bethesda, Maryland, United States, 20814
      • Suburban Hospital
  • Michigan
    • Midland, Michigan, United States, 48670
      • Mid Michigan Cardiovascular Research
    • Petoskey, Michigan, United States, 49770
      • Cardiac & Vascular Research Center of Northern Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Bryan Heart
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Lindner Research Center, The Christ Hospital
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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	Drug: 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
Proportion of subjects developing AKI as defined by the AKIN criteria	Baseline through Day 5

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Quark Pharmaceuticals
• Investigators: Study Director: Elizabeth Squiers, M.D., Quark Pharmaceuticals

Publications and helpful links

General Publications

• Thielmann M, Corteville D, Szabo G, Swaminathan M, Lamy A, Lehner LJ, Brown CD, Noiseux N, Atta MG, Squiers EC, Erlich S, Rothenstein D, Molitoris B, Mazer CD. Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study. Circulation. 2021 Oct 5;144(14):1133-1144. doi: 10.1161/CIRCULATIONAHA.120.053029. Epub 2021 Sep 3.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): April 1, 2018

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): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: AKI
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: QRK209