Recombinant Alpha-1-Microglobulin (RMC-035) to Prevent Acute Kidney Injury in Cardiac Surgery Patients: Phase 1b Evaluation of Safety and Pharmacokinetics

INTRODUCTION: Acute kidney injury (AKI) is a common complication in cardiac surgery patients and prevention is needed to improve clinical outcomes. Alpha-1-microglobulin (A1M) is a physiological antioxidant with strong tissue-protective and cell-protective properties that has demonstrated renoprotective effects. RMC-035, a recombinant variant of endogenous human A1M, is being developed for the prevention of AKI in cardiac surgery patients. METHODS: In this phase 1b, randomized, double-blind, and parallel group clinical study, 12 cardiac surgery patients undergoing elective, open-chest, on-pump coronary artery bypass graft and/or valve surgery with additional predisposing AKI risk factors were enrolled to receive in total 5 intravenous doses of either RMC-035 or placebo. The primary objective was to evaluate the safety and tolerability of RMC-035. The secondary objective was to evaluate its pharmacokinetic properties. RESULTS: RMC-035 was well tolerated. The nature and frequency of adverse events (AEs) were consistent with the expected background rates in the underlying patient population with no AEs reported as related to study drug. No clinically relevant changes were observed for vital signs or laboratory parameters except for renal biomarkers. Several established AKI urine biomarkers were reduced at 4 hours after first dose administration in the treatment group, indicating a reduced perioperative tubular cell injury following RMC-035 treatment. CONCLUSION: Multiple intravenous doses of RMC-035 were well tolerated in patients undergoing cardiac surgery. Observed RMC-035 plasma exposures were safe and in the range of expected pharmacological activity. Furthermore, urine biomarkers suggest reduced perioperative kidney cell injury, warranting further investigation of RMC-035 as a potential renoprotective treatment.