Safety and Efficacy of EXO-CD24 in Preventing Clinical Deterioration in Patients With Mild-Moderate ARDS

Study Overview
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Brief Summary
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This is phase IIb, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Exosomes Overexpressing CD24 of one dose 10^10 exosome particles, to Prevent Clinical Deterioration in Patients with Mild-Moderate ARDS

Detailed Description
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The study population will include patients with mild-moderate ARDS and laboratory markers predictive of the cytokine storm, who have provided an informed consent. 90 patients will be initially screened, randomized and stratified by center in a 2:1 ratio to receive either 1010 exosome particles (60 patients) or placebo (30 patients). Study drug will be delivered using standard jet nebulizer that produce aerosol particles size of 0.4-4.4 µm. The exosomes will be diluted in 1.5 ml normal saline for inhalation, administered twice a day (bid) 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.

Official Title
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A Phase IIb, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Exosomes Overexpressing CD24 to Prevent Clinical Deterioration in Patients With Mild-Moderate ARDS

Conditions
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ARDS

Intervention / Treatment
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* Drug: EXO-CD24
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Direct and indirect lung injury etiology Age ≥18 years Patients with Early Acute Lung Injury (EALI) > 2 ,or patient on HFNC/NIPPV [(1 point for an oxygen requirement > 2 to 6 liters/min or 2 points for > 6 liters/min; 1 point each for a respiratory rate ≥ 30 breaths/min and baseline immune suppression) (immune system compromised by exogenous drug etc.)] (For saturation goal >90%) [1], or ARDS diagnosis (mild/moderate) Willing and able to sign an informed consent, or has a legal guardian who is able to sign Exclusion Criteria: Any concomitant illness that, based on the judgment of the investigator might affect the interpretation or the results of the study (immunodeficiency, primary immune deficiency due to virus, hematological malignancy etc.) Patients with SaO2/FiO2<150 Patients with mechanical ventilation (ECMO). Pregnancy [positive urine pregnancy test (women of childbearing potential only)] or breastfeeding Participation in any other interventional study in the last 30 days or within 5 half-lives of receiving an investigational agent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a two arms study; one arm will receive 10^10 dose of exosomes overexpressing CD24, and the second arm will receive Placebo dose
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: investigational drug EXO-CD24 at a dose of 10^10<br>60 patients who will receive a 5-day treatment with the investigational drug EXO-CD24 at a dose of 10^10 | Drug: EXO-CD24<br>* Twice a day for 5 days, dose 10^10<br>* Other names: Exosomes Overexpressing CD24;|
| Placebo Comparator: Group 2: treatment in a clean sterile saline solution (placebo)<br>30 patients who will receive a 5-day treatment in a clean sterile saline solution (placebo) | Other: Placebo<br>* Twice a day for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of participants with treatment-related adverse events as assessed by CTCAE v.5 during the 28 days of the study. |  | 28 days | 
| Efficacy: the rate of hypoxemic respiratory failure (reported as S/F<150) at day 7 |  | 7 days | 
| Efficacy: the rate of hypoxemic respiratory failure (reported as S/F<150) at day 28 |  | 28 days |