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: 21.1Level: PTClassification code 10069339Term: Acute kidney injurySystem 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-AT
• Lead Sponsor: Quark Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-04
• Last Update Posted: 3 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• 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 failure
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 sitespecific
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 nursi

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 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

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: • To assess the efficacy of a single intravenous (IV) infusion of QPI-1002 in preventing Major Adverse Kidney<br>Events (MAKE) in subjects at high risk for acute kidney injury (AKI) following cardiac surgery.<br>• To assess the safety and tolerability of an IV infusion of QPI-1002 in comparison to placebo when<br>administered to subjects at high risk for AKI following cardiac surgery.;Secondary Objective: Not applicable<br>;Primary end point(s): Primary Efficacy Endpoint <br>1. Proportion of subjects who develop any of the components of MAKE90, defined as either:<br>• Death through day 90<br>• Initiation of Renal Replacement Therapy (RRT) through day 90, or<br>• A = 25% reduction in eGFR at the Day 90 visit<br>Note: For the primary analysis, eGFR will be based on serum cystatin C (eGFRcys). Estimated GFR based on serum creatinine (eGFRcreat) will be used in a sensitivity analysis<br>;Timepoint(s) of evaluation of this end point: Through Day 90

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key Secondary Efficacy Endpoints <br>1. Proportion of subjects developing AKI overall by modified Acute Kidney Injury Network (AKIN) criteria within 5 days post-surgery by SCr<br>2. Proportion of subjects who develop any of the components of MAKE90, defined as either:<br>• Death through day 90<br>• Initiation of RRT through day 90, or<br>• A = 25% reduction in eGFR at the Day 90 visit<br>Note: This secondary analysis is identical to the primary efficacy analysis except that it will include all<br>subjects regardless of age. Thus, eGFRcys will be used for this analysis. eGFRcreat will be used in a<br>sensitivity analysis.<br>3. Proportion of subjects developing AKI within 5 days post-surgery as defined by modified AKIN criteria stage 2 and stage 3 combined by SCr<br>4. Proportion of subjects who develop either or both of the following:<br>• Death through day 90<br>• Initiation of RRT through day 90<br>;Timepoint(s) of evaluation of this end point: Through Day 90