a phase ii randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of exosomes overexpressing cd24 to prevent clinical deterioration in patients with moderate or severe covid-19 infection

Conditions: COVID-19 Disease

Summary: a phase ii randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of exosomes overexpressing cd24 to prevent clinical deterioration .the study population will include patients with moderate or severe covid-19 infection and laboratory markers predictive of the cytokine storm from the corona department of each site, who have provided an informed consent. 155 patients will be randomized in a 2:1 ratio to receive either 1010 exosome particles (103 patients) or placebo (52 patients).the exosomes will be diluted in 4ml normal saline for inhalation, administered once daily (qd) for 5 days. placebo (saline) will be prepared for inhalation and administered in the same manner as the exosomes.

the exosomes will be diluted in 4ml normal saline for inhalation, administered once daily (qd) for 5 days. placebo (saline) will be prepared for inhalation and administered in the same manner as the exosomes. study treatments will be given as add-on to standard of care. following the 5 days of treatment, patients will remain in follow-up for 23 additional days. patients who will be discharged before the end of the 5-day treatment period will continue to receive treatment at home. treatment administration and the study assessments will be carried out by the research personnel at the home of the patient, implementing the required protective measures. on day 28, when the isolation period is completed, these patients will arrive at the study site for the follow-up visit.

Eligibility criteria:
inclusion criteria: 1. a covid-19 diagnosis confirmed with a sars-cov-2 viral infection positive polymerase chain reaction (pcr) test 2. age 18-80 years 3. severity of disease according to the following criteria (at least one clinical parameter and one laboratory parameter are required): a. clinical and imaging-based evaluation i. respiratory rate \> 23/min and \ 50% within 24-48 hours or a severe deterioration compared to imaging at admission b. evidence of an exacerbated inflammatory process i. ldh score\> 450 u/l ii. crp \>50 mg/l iii. ferritin \>1650 ng/ml iv. lymphocytes \>800 cells/mm3 v. d-dimers \>1 mcg/ml 4. willing and able to sign an informed consent exclusion criteria: 1. age\ 80 years 2. any concomitant illness that, based on the judgment of the investigator is terminal 3. ventilated patient 4. pregnancy (positive urine pregnancy test \[women of childbearing potential only\]) or breastfeeding 5. patients with immunodeficiency (eg, cll, hiv, rituximab therapy) 6. unwilling or unable to provide informed consent 7. participation in any other interventional study in the last 30 days

Keywords: ae- adverse event bun - blood urea nitrogen ci- confidence interval cmp - clinical monitoring plan consort- consolidated standards of reporting trials crf - case report form damp- damage-associated molecular patterns dmem- dulbecco's modified eagle's medium gcp - good clinical practice gmp- good manufacturing practice gvhd- graft-versus-host disease hct - hematopoietic stem cell transplantation ich- international conference on harmonization idsa- infectious diseases society of america irb- institutional review board itt- intend-to-treat analysis set mitt- modified intent-to-treat analysis set nlr - neutrophil-to-lymphocyte ratio pcr - polymerase chain reaction pi- principal investigator pp- per-protocol analysis set sa- safety analysis set sae- serious adverse event soa- schedule of activities tlr- toll-like receptors