Safety and Efficacy of Exosomes Overexpressing CD24 in Two Doses for Patients With Moderate or Severe COVID-19

A Phase II Randomized, Single-blind Dose Study to Evaluate the Safety and Efficacy of Exosomes Overexpressing CD24 in 10^9 Dose Versus 10^10 Dose, for the Prevention of Clinical Deterioration in Patients With Moderate or Severe COVID-19

This is a phase II randomized, single-blind dose study to evaluate the safety and efficacy of exosomes overexpressing CD24 of two doses, Dose 1 - 10^9 exosome particles (per dose) versus Dose 2 - 10^10 exosome particles (per dose), to prevent clinical deterioration in patients with Moderate or Severe COVID-19 infection.

The study population will include patients with moderate or severe COVID-19 and laboratory markers predictive of the cytokine storm, who have provided an informed consent.

90 patients will be randomized in a 1:1 ratio to receive either 109 exosome particles (45 patients) or 1010 exosome particles (45 patients).

The exosomes will be diluted in normal saline for inhalation via mouthpiece nebulization, administered once daily (QD) for 5 days.

Study treatments will be given as an add-on to the standard of care. Following the 5 days of treatment, patients will remain in follow-up for 23 additional days. In case of hospital discharge before the full follow-up planned, the patient will be required to return to the site for completion of all study assessments.

Inclusion Criteria:

1. A COVID-19 diagnosis confirmed with a SARS-CoV-2 infection positive polymerase chain reaction (PCR) within 30 days of screening.

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 < 30/min ii. SpO2 at room air ≤94% and ≥90% iii. Bilateral pulmonary infiltrates >25% within 24-48 hours or a severe deterioration compared to imaging at admission.

   b. Evidence of an exacerbated inflammatory process i. LDH > 300 U/L or what is the upper limit for normal per age ii. CRP >25 mg/L iii. Ferritin >500 ng/ml iv. Lymphocytes <800 cells/mm3 v. D-dimers > 500ng/ml

4. Willing and able to sign an informed consent.

Exclusion Criteria:

1. Any concomitant illness that, based on the judgment of the Investigator might affect the interpretation or the results of the study (i.e., immunodeficiency).
2. Mechanically-ventilated patient or patient who will probably require ICU admission or mechanical ventilation within 24 hours from enrolment, according to the Investigator's judgment.
3. Previous complete or partial vaccination for SARS-CoV-2.
4. Pregnancy [positive urine pregnancy test (women of childbearing potential only)] or breastfeeding.
5. Participation in any other Interventional study in the last 30 days
6. Active cancer.