Abstract: FR-PO077
Design of the 1128-CL-0201 Study: A Phase 2 Proof of Concept, Double-Blind, Randomized, Placebo-Controlled Study of ASP1128 in Patients at Risk for AKI After Cardiac Surgery
Session Information
- AKI: Clinical Outcomes, Trials
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Van till, Olivier, Astellas Pharma Inc., Tokyo, Japan
- Renfurm, Ronny, none, Rotterdam, Netherlands
- Mulligan, George, Mitobridge Inc., Cambridge, Massachusetts, United States
- Tozzo, Effie, Mitobridge, an Astellas company, Cambridge, Massachusetts, United States
- Kameoka, Chisato, Astellas Pharma Inc., Tokyo, Japan
- Molitoris, Bruce A., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Shaw, Andrew, University of Alberta, Edmonton, Alberta, Canada
- Engelman, Daniel, Baystate Medical Center, Springfield, Massachusetts, United States
- Kellum, John A., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Background
AKI occurs in approximately 20-30% of cardiac surgery patients, but can reach 70% in high risk or biomarker-defined populations. No treatments are approved to treat AKI. ASP1128 is a peripherally active selective modulator of PPARd that improves metabolic and mitochondrial function. In AKI animal models, ASP1128 ameliorated renal function, histopathology, and injury biomarkers. It was shown to be safe in healthy human volunteers.
Methods
This is a randomized, double-blind, placebo-controlled, proof-of-concept, phase IIa study, to be conducted in patients at risk for AKI following cardiac surgery. A maximum of 220 patients will be randomized at ∼40 sites in North America. The study comprises three parts: 1) pre-surgery screening period, 2) CABG and/or valve surgery, and 3) post-surgery double-blind treatment period with a 90-day follow-up. To evaluate patient outcomes, patients with moderate/severe risk of AKI (based on urinary biomarkers TIMP-2/IGFBP-7) at 2-6 hours post-surgery will be randomized, while the biomarker negative patients will be followed-up as an observational standard-of-care cohort. Randomized patients will receive ASP1128 (n=110) or matching placebo (n=110) IV once daily for 3 days. Primary end point: %patients developing AKI based on KDIGO serum creatinine criteria within 72 hours post-surgery. Secondary endpoints include AKI rate based upon all KDIGO criteria and within 7 days, as well as Major Adverse Kidney Events (defined as all-cause mortality, renal replacement therapy, and/or ≥ 25% sustained reduction in eGFR) within 30 and 90 days.
Ethics:
This study is approved by the relevant institutional review boards/independent ethics committees and conducted in accordance with the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Trial registration: NCT03941483.
Results
Study results are expected in the second half of 2020.
Conclusion
The Aim of this study is to develop a short-term early intervention treatment for AKI to improve patient outcomes following cardiac surgery. The study will provide insight into the role of mitochondrial injury and fatty-acid oxygenation in propagating AKI.
Funding
- Commercial Support – Astellas Pharma Inc.