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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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
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COVID-19 Disease

Intervention / Treatment
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* Drug: Exosomes overexpressing CD24


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A COVID-19 diagnosis confirmed with a SARS-coV-2 viral infection positive polymerase chain reaction (PCR) test Age 18-80 years 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 >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 Willing and able to sign an informed consent Exclusion Criteria: Age<18 years or >80 years Any concomitant illness that, based on the judgment of the Investigator is terminal Ventilated patient Pregnancy (positive urine pregnancy test [women of childbearing potential only]) or breastfeeding Patients with Immunodeficiency (eg, CLL, HIV, rituximab therapy) Unwilling or unable to provide informed consent Participation in any other Interventional study in the last 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1010 Exosome<br>103 patients will receive either 1010 exosome particles. | Drug: Exosomes overexpressing CD24<br>* The suggested therapeutic agent here is based on an existing therapeutic platform that uses exosomes that were engineered to overexpress CD24 that can directly suppress the cytokine storm. The exosomes will be isolated and purified from human embryonic kidney T-REx™-293 cells that constitutively express high levels of human CD24.<br>|
| Placebo Comparator: Placebo<br>52 patients will receive placebo- saline. | Drug: Exosomes overexpressing CD24<br>* The suggested therapeutic agent here is based on an existing therapeutic platform that uses exosomes that were engineered to overexpress CD24 that can directly suppress the cytokine storm. The exosomes will be isolated and purified from human embryonic kidney T-REx™-293 cells that constitutively express high levels of human CD24.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of EXO-CD24 in the treatment of patients with moderate or severe COVID-19 disease |  | One year | 
| To assess the efficacy of EXO-CD24 in the clinical improvement of COVID-19 disease |  | One year | 
| To evaluate respiratory failure (defined as the need for mechanical ventilation, ECMO, non-invasive ventilation, or high-flow oxygen devices) rate. |  | One year | 
| To evaluate the death rate. |  | One year | 
| To evaluate time to improvement and recovery (COVID-19 clinical severity score of 3 or lower). |  | One year | 
| To evaluate time from hospitalization to hospital discharge. |  | One year | 
| To assess the COVID-19-related symptoms using patient-reported outcome measure (PRO) score. |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of EXO-CD24 on the respiratory rate. |  | One year | 
| To evaluate the effect of EXO-CD24 on the change in blood oxygen saturation (SpO2). |  | One year | 
| To evaluate the effect of EXO-CD24 on the proportion of patients requiring ventilation. |  | One year | 
| To evaluate the effect of EXO-CD24 on the level of inflammatory markers (eg, CRP, ferritin, fibrinogen, di-dimers, IL-6, LDH, lymphocytes count. |  | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GCP - Good Clinical Practice, GMP- Good Manufacturing Practice, GVHD- Graft-versus-host disease, HCT - Hematopoietic stem cell transplantation, NLR - Neutrophil-to-lymphocyte ratio, 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, SoA- Schedule of Activities, TLR- Toll-like receptors, AE- Adverse event, BUN - Blood urea nitrogen, CI- Confidence Interval, CMP - Clinical monitoring plan, SA- Safety analysis set, SAE- Serious adverse event, CONSORT- Consolidated Standards of Reporting Trials, CRF - Case Report Form, DAMP- Damage-associated molecular patterns, DMEM- Dulbecco's Modified Eagle's Medium, PCR - Polymerase chain reaction, PI- Principal Investigator, PP- Per-Protocol analysis set