Abstract
Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920 ), which was aimed to define the appropriate schedule and dosage of LEAF-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.
Keywords: COVID-19; Clinical trial; Drug delivery; Nanomedicine; Sepsis.
【저자키워드】 COVID-19, clinical trial, Sepsis, drug delivery, breath, nanomedicine, 【초록키워드】 ARDS, Open-label, intensive care, acute respiratory distress syndrome, intensive care unit, Respiratory complications, oxygen, Sepsis, drug, in vitro, outcome, clinical outcomes, Clinical outcome, mice, endothelial cells, clinical, nanomedicine, multicenter, patients, half-life, acute respiratory distress, Concentration, dose, phase, COVID-19 patient, Oxygenation, respiratory distress, trans-crocetin, Tolerability, dosage, therapeutic efficacy, syndrome, EudraCT, leaf, Therapeutic treatment, clinical activity, vascular tissue, current, ENhance, IMPROVE, healthy, injected, treated, demonstrated, to define, impacted, 【제목키워드】 mechanical ventilation, Patient, encapsulation, ENhance, receiving,