Phase 3 Study to see if QPI-1002 is effective and safe for the Prevention of Acute Kidney Injury in Subjects at High Risk for AKI following Cardiac Surgery

Phase 1

• Conditions: QPI-1002 is being developed for prevention of acute kidney injury (AKI) in patients at risk for AKI following cardiac surgery and for reduction in the incidence and severity of delayed graft function after kidney transplantation.; MedDRA version: 21.1 Level: PT Classification code 10069339 Term: Acute kidney injury System Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

• Registration Number: EUCTR2018-000757-49-GB
• Lead Sponsor: Quark Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-30
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 1088

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, with or without hypothermic circulatory arrest:
a) Combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve (valve(s) surgery)
b) Only CABG or single valve surgery that is a redo” surgery (i.e. subject had any previous open chest cavity cardiovascular surgery)
c) Surgery of more than one cardiac valve (valve surgery)
d) Surgery of the aortic root or ascending part of the aorta in combination with CABG and/or valve(s)
surgery
e) If only CABG or single valve surgery and that surgery is not a redo” surgery (i.e. not the surgery described in Inclusion Criteria #5b), subjects are required to have at least one additional risk factor for AKI: either one additional risk factor from Inclusion Criterion #4 above (for a total of two risk factors from Inclusion Criterion #4 above), OR age = 65 years old, OR history of congestive heart failur requiring hospitalization, OR type 2 diabetes requiring at least 1 oral hypoglycemic agent but not requiring insulin
Note: Transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR) are allowed only if performed in combination with surgeries defined in Inclusion Criterion #5.
*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.
6. No known cancer as identified by cancer screening according to site-speci

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 for subjects = 45 years old.(Cardiac Surgery off CPB for subjects < 45 years old is allowed.)
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 Criterion #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 t

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified