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

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02610283
• Other study ID #: QRK209
• Status: Completed
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: April 2018

Study information

• Verified date: April 2018
• Source: Quark Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 341
• Est. completion date: April 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

Drug:
• QPI-1002
IV injection
• Placebo
isotonic saline

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Quark Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects developing AKI as defined by the AKIN criteria		Baseline through Day 5
Secondary	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