#644 A phase 2b dose finding study to assess the efficacy of RMC-035 on renal function in participants at high risk for kidney injury following open-chest cardiac surgery (POINTER)

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Abstract Background and Aims Acute kidney injury (AKI) is a common and serious complication of cardiac surgery, potentially leading to the onset or progression of CKD. There are no approved pharmacotherapies for the prevention of AKI or the subsequent development or progression of CKD. RMC-035, a therapeutic variant of the endogenous protein alpha-1-microglobulin, demonstrates nephroprotective effects in numerous preclinical disease models1. Results from the Phase 2a AKITA trial2 indicate that RMC-035 improves long-term kidney outcomes after cardiac surgery. The Phase 2b POINTER trial aims to confirm the findings from AKITA and identify the optimal RMC-035 dose prior to initiating a pivotal Phase 3 study. Method POINTER (NCT06475274) is an international, multicenter, randomized, placebo-controlled, double-blind trial. A total of approximately 160 high-risk patients scheduled for open-chest cardiac surgery with cardiopulmonary bypass (CPB) will be recruited in Europe and Canada. Two RMC-035 dose levels (30 and 60 mg) will be compared with placebo. Study drug will be administered by IV infusion 10 min before CPB, and at 6- and 24-h post-surgery. Patients will be followed daily until day 4, and on days 7, 60, and 90. The primary endpoint is the change in eGFR at day 90 compared to baseline. A key secondary endpoint is major adverse kidney events on day 90 (MAKE90). Other secondary endpoints include the occurrence of AKI, and plasma concentrations of RMC-035. Safety will be assessed by treatment-emergent adverse events, vital signs, electrocardiogram and routine blood biochemistry and hematology parameters. Results Not applicable. Conclusion In the completed AKITA trial, RMC-035 improved eGFR by day 90 vs placebo, and fewer patients treated with RMC-035 met the secondary MAKE90 endpoint. The eGFR benefit was more pronounced in the predefined subgroup of patients with lower preoperative eGFR (<60 mL/min/1.73 m²). Herein, we present the design of the Phase 2b POINTER trial, aimed at determining the optimal dosing regimen of RMC-035 and confirming its nephroprotective properties prior to a Phase 3 trial. The results are expected to advance our understanding of novel therapeutic strategies for the prevention of AKI and permanent loss of renal function in patients at high risk for AKI following cardiac surgery.

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