George Mulligan, PhD, discusses during Kidney Week the results of a phase IIa study showing potential in a new drug to treat patients at risk for developing an acute kidney injury following cardiovascular surgery.
George Mulligan, PhD
Acute kidney injuries (AKI) occur in approximately 20-30% of cardiac surgery patients, with the prevalence reaching as high as 70% in high risk or biomarker-defined populations.
To cut down on this rate, investigators are testing a new drug, ASP1128, to ameliorate renal function, histopathology, and injury biomarkers. The drug is a peripherally active selective modulator of PPARd that improves metabolic and mitochondrial function.
George Mulligan, PhD, senior vice president of Translational Medicine at Mitrobridge, explained the approach of the study and future plans for ASP1128 in an interview with MD Magazine® during the American Society of Nephrology (ASN) Kidney Week in Washington, D.C.
MD Magazine: What do you believe the main take-home point of the study is?
Mulligan: The study is an ongoing phase II trial of patients at risk for AKI after cardiovascular surgery.
We're evaluating a mitochondrial-based therapy for the treatment of patients coming out of surgery who may be at risk of an AKI event. And we're measuring those AKI events at 3-days post-surgery.
It's a randomized control study, in which we compare placebo to 1128. And we're looking to see if we can reduce the rates of AKI, in this particular hospital setting.
MD Magazine: What is the methodology for how you completed the study?
Mulligan: This clinical trial is ongoing now, we're enrolling patients at 40 centers across the United States.
And we're interestingly taking the approach of enriching for subjects who are at high risk for AKI by collecting biomarker data shortly after their cardiovascular surgery, and then identifying the patients who are at high or low risk for an AKI event.
The low risk patients, we really don't want to over treat those subjects. Those patients are kept in an observational cohort, whereas the patients who are at higher risk for AKI are randomized into placebo or 1128.
Then they're treated for 3-days with the IV formulation drug. And after that time point, we measure AKI and then we have long-term follow up for 90 days to see if there are consequences including loss of kidney function, death or dialysis, but those are make criteria for major adverse kidney events.
MD Magazine: What are the future clinical plans for ASP1128?
Mulligan: This is a phase IIa study, which we consider as proof of concept. Can we address the unmet medical need and show with some significance that there's an improvement so we're characterizing early efficacy as well as safety.
This study can then lead to, if positive, a pivotal study that would be larger with perhaps a more diverse group of patients, and would provide the basis for registration in that setting at Astellas (Pharma) with our global capabilities. We would consider doing it the US, but it may also rapidly become a global study which could support registration in multiple geographies.