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

Sponsor

Quark Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02610283

Collaborator

(none)

341

Enrollment

Locations

Arms

Duration (Months)

9.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Drug: QPI-1002 Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

341 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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

Study Start Date :

Dec 1, 2015

Actual Primary Completion Date :

Feb 1, 2018

Actual Study Completion Date :

Apr 1, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: QPI-1002

QPI-1002 Injection, single dose

Drug: QPI-1002

IV injection

Placebo Comparator: Placebo

isotonic saline

Drug: Placebo

isotonic saline

Outcome Measures

Primary Outcome Measures

Proportion of subjects developing AKI as defined by the AKIN criteria [Baseline through Day 5]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.)

Contacts and Locations

Locations

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

Sponsors and Collaborators

Quark Pharmaceuticals

Investigators

Study Director: Elizabeth Squiers, M.D., Quark Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Quark Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT02610283

Other Study ID Numbers:

QRK209

First Posted:

Nov 20, 2015

Last Update Posted:

Jan 10, 2019

Last Verified:

Apr 1, 2018

Keywords provided by Quark Pharmaceuticals

AKI

Additional relevant MeSH terms:

Acute Kidney Injury

Wounds and Injuries

Study Results

No Results Posted as of Jan 10, 2019