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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Drug: QPI-1002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: QPI-1002<br>QPI-1002 Injection, single dose | Drug: QPI-1002<br>* IV injection<br>|
| Placebo Comparator: Placebo<br>isotonic saline | Drug: Placebo<br>* isotonic saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects developing AKI as defined by the AKIN criteria |  | Baseline through Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AKI