Abstract: SA-OR124
Efficacy and Safety of QPI-1002 (QPI) for Prevention of AKI Following Cardiac Surgery
Session Information
- High-Impact Clinical Trials
November 02, 2017 | Location: Hall J, Morial Convention Center
Abstract Time: 11:15 AM - 11:30 AM
Category: Acute Kidney Injury
- 003 AKI: Clinical and Translational
Authors
- Corteville, David, McLaren Northern Michigan, Petoskey, Michigan, United States
- Still, Robert J, JCCR, Jacksonville, Florida, United States
- Szabo, Gabor, University of Heidelberg, Heidelberg, Germany
- Swaminathan, Madhav, Duke University Medical Center, Durham, North Carolina, United States
- Jayasankar, Vasant, Cardiothoracic and Vascular Surgical Assoc, Jacksonville, Florida, United States
- Lamy, Andre, McMaster University, Hamilton, Ontario, Canada
- Lehner, Lukas J, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Thielmann, Matthias, West-German Heart and Vascular Center Essen, University Duisburg-Essen, Essen, Germany
- Brown, Craig D, New Brunswick Heart Centre, Saint John, New Brunswick, Canada
- Squiers, Ec, Quark Pharmaceuticals, Inc., Fremont, California, United States
- Schwertschlag, U., Quark Pharmaceuticals, Inc., Fremont, California, United States
- Potts, A, Quark Pharmaceuticals, Inc., Fremont, California, United States
- Patel, A, Quark Pharmaceuticals, Inc., Fremont, California, United States
- Messersmith, E K, Quark Pharmaceuticals, Inc., Fremont, California, United States
- Rothenstein, D, Quark Pharmaceuticals, Inc., Fremont, California, United States
- Odenheimer, D J, Quark Pharmaceuticals, Inc., Fremont, California, United States
- Erlich, S, Quark Pharmaceuticals, Inc., Fremont, California, United States
Group or Team Name
- QRK209 AKI Study Group
Background
QPI, a siRNA targeting p53, is being developed for prevention of Delayed Graft Function (DGF) following renal transplantation (ReGIFT Phase 3 Study, NCT#02610296) and for acute kidney injury (AKI). AKI is a major complication of cardiac surgery (CS) that increases morbidity and mortality. No treatments are approved for the prevention of AKI following CS.
Methods
The efficacy and safety of QPI, was studied in a global Phase 2 double-blind study (N=341: QPI=165, Placebo (PL)=176) undergoing CS at 41 sites (NCT#02610283). Subjects undergoing non-emergent CS at risk for AKI were enrolled (risk factors included: Age ≥ 70 years; eGFR ≤ 60 mL/min/1.73m2, diabetes, proteinuria, congestive heart failure). Subjects were stratified by eGFR (≥ vs < 60mL/min/1.73m2). A single IV dose of either QPI (10mg/kg) or PL was given 4 hours post-CS. Safety assessments included clinical and laboratory exams and adverse events (AEs). Efficacy endpoints included the rate of AKI determined by serum creatinine according to AKIN (primary), RIFLE and KDIGO (secondary) criteria assessed through Day 5. Secondary endpoints also included duration and grade of AKI, and the composite of death, renal replacement therapy (RRT) and 25% reduction of eGFR at Day 90.
Results
Demographics and AE profiles were similar between treatment groups and consistent with CS. QPI treatment resulted in a 26% relative risk reduction (RRR) of AKI (AKIN): (37% QPI vs. 50% PL; p=0.020). Risk reductions were consistently observed across predefined populations (age, diabetes, CS type, gender, baseline eGFR). Treatment with QPI improved AKI across all AKIN grades (by 18%–61%; p=0.012). Duration of AKIN AKI from Days 0-5 was shorter with QPI (p=0.013). QPI significantly impacted AKI incidence, grade and duration by RIFLE and KDIGO criteria. The composite of Death, RRT and Reduction of eGFR by 25% at Day 90 favored QPI in a subpopulation (N=241) with either proteinuria, and/or low base line eGFR, and/or diabetes, (37% QPI vs 51% PL; RRR=29%; p=0.024).
Conclusion
In this study, QPI reduced the incidence, grade and duration of AKI in high risk subjects following CS. Further development of QPI for the prevention of AKI is warranted.
Funding
- Commercial Support –