1153. Safety and Potential Efficacy of Exosomes Overexpressing CD24 (EXO-CD24) for the Prevention of Clinical Deterioration in Patients with Moderate or Severe COVID-19: A Phase II, Randomized, Single-blinded Study.

BACKGROUND: EXO-CD24 is a novel inhaled drug of exosomes displaying CD24, a protein with anti-inflammatory properties. We evaluated the safety and potential efficacy of EXO-CD24, in a phase II, randomized, single-blinded clinical trial of EXO-CD24 in hospitalized patients with moderate or severe COVID-19, following the preliminary safety and efficacy results of a phase 1 study (ClinicalTrials.gov: NCT04747574). METHODS: Two tertiary care hospitals in Athens, Greece participated. Patients received either 10(9) or 10(10) exosome particles per dose, once per day for 5 days and were followed for 28 days. Safety and efficacy measures (including respiratory rate < 23 b/min and pulse oximetry SpO(2)≥ 94% on room air, oxygen need and levels of inflammatory biomarkers i.e. CRP, LDH, ferritin, fibrinogen and d-dimers) were compared between groups at days 3, 5 and 7. A separate analysis was conducted comparing the clinical course of treated patients with that of a control cohort (n=70 patients) matched by propensity scoring out of a similar period hospitalized cohort (n=202) that did not participate in the study. RESULTS: Between June 9th and August 3rd 2021, 91 patients underwent randomization: 45 in group A and 46 in group B (10(9)vs. 10(10) exosome particles per dose). Mean age was 49.4 (± 13.2) years and 74.4% were male. Mean time from symptom onset to randomization was 8 days. Improvement in respiratory rate and pulse oximetry was noted in 72 out of 86 (83.7%) and 55 out of 86 (64%) analyzed patients. Day 7 inflammatory indices levels dropped at least 50% from baseline admission values in 72 out of 86 (82.8%) analyzed patients (p< 0.001). No treatment-related adverse events were reported. Comparison with the propensity score matched group showed statistically significant differences in the same parameters (p≤ 0.01 for all comparisons). CONCLUSION: Our results suggest safety and potential efficacy of EXO-CD24 on clinical and laboratory parameters of moderate or severe COVID-19, that deserve further investigation in a phase 3 study. (Funded by Athens Medical Society. ClinicalTrials.gov: NCT04902183, EU Clinical Trials Register EudraCT Number 2021-002184-22). DISCLOSURES: All Authors: No reported disclosures.