LEAF- 4L6715 enhances oxygenation in patients with acute respiratory distress syndrome (ARDS) due to severe COVID-19: Final results of a phase I/II clinical trial

LEAF-4L6715 is a liposomal formulation encapsulating transcrocetin (TC) developed to enhance the diffusion of oxygen in the body. Here, we report the final results of the phase I/II clinical trial (NCT04378920; EUDRACT2020-001393-30) initiated to identify an optimal regimen and to assess the activity of TC in the context of acute respiratory distress syndrome (ARDS). More specifically, LEAF-4L6715 was developed to treat patients with ARDS due to severe SARS-CoV-2 infection who have a ratio of partial arterial pressure to inspired fraction of oxygen (PaO2/FiO2 ratio) <200 treated with artificial ventilation support in an intensive care unit. A total of 37 patients were treated (across 6 dosing cohorts) with LEAF-4L6715 given as an intravenous infusion for over 90 minutes. The dose of LEAF-4L6715 was increased until the transaminase levels were elevated and 4 grade 3 events occurred among 8 patients. The recommended dosage was determined to be a fixed concentration of 300 mg administered every 12 hours. An improvement in the PaO2/FiO2 ratio and SOFA score was observed. The overall 28-day survival rate of 81%. This study identified the recommended dose for LEAF 4L6715 and the dose-limiting toxicity and showed an overall favorable risk/benefit profile. These preliminary findings are promising for the activity of LEAF-4L6715 but will require confirmation in a randomized phase III trial.