Principal Investigator: Craig Selzman
Keywords: Cardic Surgery , Acute Kidney Injury , Prevention Department: Cardiothoracic Division
IRB Number: 00115699 Co Investigator: Jason Glotzbach
Specialty: Cardiology
Sub Specialties: Preventive Cardiology
Recruitment Status: Recruiting

Contact Information

Carlyn Sander
carlyn.sander@hsc.utah.edu
8015875727

Brief Summary

Purpose: 

The purpose of this Phase 3 study is to characterize the efficacy and safety of QPI-1002 for
prevention of Major Adverse Kidney Events (MAKE) in subjects who are at high risk for AKI
following cardiac surgery. The primary endpoint will be the proportion of subjects who develop
any of the components of MAKE90 (MAKE by day 90), defined as either death through day 90,
initiation of Renal Replacement Therapy (RRT) through day 90, or a ≥ 25% reduction in
estimated glomerular filtration rate based on serum cystatin C (eGFRcys) at the Day 90 visit.

Objectives

• To assess the efficacy of a single intravenous (IV) infusion of QPI-1002 in preventing Major Adverse Kidney
Events (MAKE) in subjects at high risk for acute kidney injury (AKI) following cardiac surgery.
• To assess the safety and tolerability of an IV infusion of QPI-1002 in comparison to placebo when
administered to subjects at high risk for AKI following cardiac surgery.

Detailed Description

Subjects who have undergone non-emergent cardiac surgery and meeting all other eligibility criteria will berandomized 1:1 after cardiac surgery to receive a blinded single infusion of either QPI-1002 (10mg/kg) or placebo(saline). The selection of a 10 mg/kg single dose of QPI-1002 is based on the results from the previouslyconducted Phase 1 QRK.002 study in cardiac surgery subjects, the Phase 1/2 QRK.006 study in recipients of akidney transplant from deceased donors, and the demonstration of a positive benefit risk with QPI-1002 forreduction of the incidence of AKI in the Phase 2 study QRK209. Study drug will be administered via intravenousbolus approximately 4 hours ± 30 minutes after the discontinuation of cardiopulmonary bypass (CPB) pump.Study enrollment is planned not to exceed approximately 1088 subjects. Approximately 1038 subjects who haveundergone cardiac surgery will be randomized with a target of 519 subjects in each treatment group. Up to anadditional 50 subjects, adults 18 to <45 years old, may be randomized. An interim safety analysis will beconducted when approximately 50% of the subjects have been randomized and complete Day 5.Subject data will be collected at the Screening Visit (up to 28 days prior to cardiac surgery), Baseline/Day −1,Surgery and Post-Op, Day 1, 2, 3, 4, 5, 7, Day of Discharge, and Days 30, 60, and 90. Long term subject survivaland malignancy status will be obtained under a separate rollover protocol at one year post dosing.Blood samples will be obtained at protocol specific times for analysis of neutrophil gelatinase-associated lipocalin(NGAL).The study duration is 90 days. The primary endpoint will be evaluated at Day 90, with multiple secondaryendpoints, including incidence, severity and duration of AKI. Hospitalization length of stay and number of posthospitalization days at the pre-hospitalization residence endpoints will be collected through Day 90 and analyzedas specified in the Statistical Analysis Plan (SAP). Adverse events (AEs) will be collected through Day 30 andserious adverse events (SAEs) will be collected through Day 90. Long term subject survival and malignancystatus will be obtained under a separate rollover protocol at one year post dosing.Data will be locked and assessed for efficacy and safety once the

Inclusion Criteria

Inclusion Criteria
1. Have the ability to understand the requirements of the study, are able to provide written informed consent
(including consent for the use and disclosure of research related health information) and are willing and able
to comply with the requirements of the study (including required study visits)
2. Adult male or female, age ≥ 18 years old
3. Have stable pre-operative renal function per Investigator assessment and no known increase in Serum
creatinine (Scr) of ≥ 0.3 mg/dL (≥ 26.4 μmol/L) during preceding 28 days as assessed by the site’s local
laboratory using standard assay methodology.
4. At risk for AKI following cardiac surgery on the basis of at least one of the following pre-operatively
assessed risk factors:
a) eGFR (defined using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Scr formula) of
< 60 mL/min/1.73 m2
b) Diabetes with ongoing insulin treatment (defined as known type 2 or type 1 diabetes requiring prescribed
insulin usage prior to hospitalization for cardiac surgery)
c) Albuminuria defined as Urine Albumin/Creatinine ratio > 30 mcg/mg or screening urine dipstick of 1+

Note: If albuminuria is the only possible risk factor (i.e. eGFR is ≥ 60 mL/min/1.73 m2 and subject does not have a history of diabetes requiring prescribed insulin usage), a dipstick must be confirmed by urinalysis as > 30 mcg albumin/mg creatinine. If the urine albumin creatinine ratio is not available, and albuminuria is the only possible risk factor, a dipstick value of ≥ 2+ for protein or equivalent may be considered as meeting the albuminuria definition (> 30 mcg albumin/mg creatinine).

5. Undergoes non-emergent open chest cavity cardiovascular surgeries, with use of cardiopulmonary bypass
(CPB) pump:
a) Combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve
(valve(s) surgery)
b) Surgery of more than one cardiac valve (valve surgery)
c) Surgery of the aortic root or ascending part of the aorta in combination with CABG and/or valve(s)
surgery
d) If only CABG or single valve surgery, subjects are required to have at least one additional risk factor for
AKI: either two risk factors from Inclusion Criteria #4 above, OR age ≥ 70 years old, OR history of
congestive heart failure requiring hospitalization
Note: Transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR)

*Note: "Non-emergent surgery" would denote an operation that does not require prompt and immediate surgery (within a few hours or the same day) and is scheduled in advance.

are allowed only if performed in combination with surgeries defined in Inclusion Criteria #5.
6. No known cancer as identified by cancer screening according to site-specific pre-operative standard of care
7. Past medical history must be negative for malignancy within 5 years of randomization, with the exception of
adequately treated basal cell or squamous cell carcinoma, or cervical carcinoma in situ
8. A female subject is eligible to enter the study if she is:
a) Not pregnant or nursing
b) Of non-childbearing potential (i.e., post-menopausal defined as having been amenorrheic for at least l
year prior to screening, or has had a bilateral tubal ligation at least 6 months prior to administration of
study drug or bilateral oophorectomy or complete hysterectomy)
c) If of childbearing potential, must have a negative urine or serum pregnancy test within 48 hours prior to
cardiac surgery and be using a highly effective means of contraception (per site-specific guidelines or
use 2 methods of birth control concurrently, whichever is more stringent), which will be continued until
the Day 90 visit
9. Male subjects with female partners of childbearing potential must agree to use an effective means of
contraception (per site-specific guidelines or use 2 methods of birth control concurrently, whichever is more
stringent), which will be continued until the Day 90 visit

Exclusion Criteria

Exclusion Criteria
1. Have an eGFR ≤ 20 mL/min/1.73 m2 (defined using CKD-EPI Scr formula)
2. Subjects with an eGFR < 60 mL/min/1.73 m2 (defined using CKD-EPI Scr formula) requiring intravascular
iodinated contrast within 48 hours of surgery initiation as defined by the planned skin incision. However,
subjects may be included if the post contrast increase in Scr is < 0.3 mg/dl (< 26.4 μmol/L) in at least 2 Scr
evaluations performed not less than 36 hours (post final dose of contrast) apart
3. Have a history of any organ or cellular transplant which requires active immunosuppressive treatment which
can interfere with kidney function
4. Emergent surgeries, including aortic dissection, and major congenital heart defects

*Note: See Inclusion #5. Also, "emergent surgeries" are defined as cardiac operations that are not elective and must be done promptly to address an immediately life-threatening condition.

5. Undergoes cardiac surgery off CPB or with hypothermic circulatory arrest
6. Undergoes TAVI or TAVR only* or single vessel, minimally invasive direct coronary artery bypass
(MIDCAB) off-pump surgeries or left ventricular assist device (LVAD) implantation
*Note: See Inclusion Criteria #5
7. Have participated in an investigational drug study in the last 30 days
8. Have a known allergy to or had participated in a prior study with small interfering ribonucleic acid (siRNA)
or prior treatment with QPI-1002
9. Have a known history of human immunodeficiency virus (HIV) infection
10. 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)
11. Have known active Hepatitis C (HCV) (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.)
12. 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)
13. Post cardiac surgery, have hemodynamic instability despite increasing doses of three types of vasopressors
and/or inotropes (see Appendix 1)
14. Perioperative or post cardiac surgery, an LVAD is inserted or anticipated (Note: Unplanned intraoperative
LVAD that is removed before the end of surgery (i.e. skin closure) is allowed.)
15. Post cardiac surgery, have bleeding >300 mL/hr requiring return to surgery or ≥3 units of packed Red Blood
Cells (RBC) in the first 2 hours post-surgery
16. Have required any of the following within 7 days prior to cardiac surgery: defibrillator, mechanical
ventilation, IABP, 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.)
17. Have required cardiopulmonary resuscitation (CPR) within 14 days prior to cardiac surgery
18. 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
19. Have total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the
upper limit of normal (ULN) at time of screening
20. Have a history of chronic liver disease (i.e. cirrhosis) and Child Pugh Class A liver disease with ALT/AST
above the upper limit of normal, or Class B or higher
21. Have a history or presence of a medical condition or disease or psychiatric condition that in the investigator’s
assessment would render the subject ineligible for study participation

22. Have planned or actual administration of methylene blue from 24 hours prior to surgery through the time of planned randomization