Supplementary Material for: Inhibition of Calcium Release-Activated Calcium (CRAC) channels to Treat Acute Kidney Injury: Design and Rationale of the KOURAGE study

Introduction: Patients with severe acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF) experience poorer outcomes, including higher rates of in-hospital mortality, relative to patients with less severe AKI, or those without associated AHRF. Zegocractin is a calcium release-activated calcium (CRAC) channel inhibitor with potent anti-inflammatory and pulmonary endothelial protective properties. Preclinical and early phase clinical studies suggest that zegocractin may be an effective agent for the treatment of AKI. Methods: KOURAGE (NCT06374797) is a multicenter, phase 2, randomized, double blind, placebo-controlled trial that aims to enroll approximately 150 patients with severe AKI and AHRF. Eligible patients will be randomized 1:1 to receive a total of five daily doses of zegocractin intravenous emulsion (Auxora™) or matching placebo. The objective is to evaluate the safety and efficacy of Auxora in patients with severe AKI, with the primary efficacy endpoint defined as the number of days alive, ventilator-free and kidney replacement therapy (KRT)-free from the start of the first infusion of the study drug through Day 30. A key secondary efficacy endpoint is the proportion of patients with major adverse kidney events at Day 90. Conclusion: The KOURAGE trial will investigate the safety and efficacy of Auxora in patients with severe AKI and AHRF.