Evaluation of the Safety of CD24-Exosomes in Patients With COVID-19 Infection

Study Overview
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Brief Summary
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This is an open-label Phase I study, four dose escalation groups, to evaluate the safety of CD24-exosomes in patients with moderate/severe COVID-19 disease. Patients with moderate/severe COVID-19 infection and factors predictive of a cytokine storm are recruited from the Corona department of the Tel Aviv Sourasky Medical Center (TASMC), who have provided informed consent are being recruited in four dose groups who will receive the exosome treatment as an add-on treatment to standard treatment.

Detailed Description
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Coronavirus disease 2019 (COVID-19) is a highly transmissible disease in the community. The main cause of clinical deterioration that leads to death is the cytokine storm in the lung. CD24 is a small heavily glycosylated GPI-anchored protein. CD24 is a key player in the vast majority of human cancers and also plays an important role in controlling the homeostatic proliferation of T cells. Hence, CD24 can negatively regulate inflammation. The treatment is a biologic therapeutic agent based on exosomes carrying CD24. The rationale for this treatment is that exosomes overexpressing CD24, isolated and purified from T-REx™-293 cells engineered to express CD24 at high levels, can suppress the cytokine storm and are delivered directly to the target organ using exosomes as a highly body-compatible delivery vehicle. This enables a strong reduction of the required dose (as opposed to systemic administration), and reduces the risk for adverse events.

Official Title
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A Phase I Feasibility Study to Evaluate the Safety of CD24-Exosomes in Patients With Moderate/Severe COVID-19 Infection

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Drug: EXO-CD24


Participation Criteria
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Eligibility Criteria
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A COVID-19 diagnosis confirmed with a SARS-CoV-2 viral infection positive polymerase chain reaction (PCR) test Disease severity: Moderate/severe according to the following criteria (at least one clinical parameter and one laboratory parameter are required): Clinical and Imaging-based evaluation Respiratory rate > 23/ min and < 30/min SpO2 at room air ≤94% and ≥90% Bilateral pulmonary infiltrates >50% within 24-48 hours or a severe deterioration compared to imaging at admission Evidence of an exacerbated inflammatory process LDH score > 450 u/L CRP >100 u/L Ferritin >1650 ng/ml Lymphopenia <800 cells/mm3 v. D-dimers>1 Willing and able to sign an informed consent Exclusion Criteria: Age<18 years or >85 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 Unwilling or unable to provide informed consent Participation in any other study in the last 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: EXO-CD24 exosome treatment<br>Group 1, 5 patients are treated with 1x10^8 exosome particles per 2 ml saline. Group 2: 5 patients are treated with 5x10^8 exosome particles per 2 ml saline. Group 3: 20 patients are treated with 1x10^9 exosomes particles per 2 ml saline. Group 4: 5 patients are treated with 1x10^10 exosomes particles per 2 ml saline. The drug is aerosolized in normal saline for inhalation and administered via a standard hospital-grade inhalation device, QD for 5 days. Study treatment is given as an add-on to the standard of care. | Drug: EXO-CD24<br>* The study active treatment is EXO-CD24 -exosomes (natural nano-sized vesicles secreted by human cells) that were engineered to overexpress CD24, aerosolized in normal saline for inhalation via a standard hospital-grade inhalation device, QD for 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary safety endpoint: Adverse events | Number of adverse events, and adverse events leading to premature study termination. | 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploratory Endpoint: Alive at Day 5 without bronchospasms, unexpected infections, or clinical deterioration | A composite endpoint comprised of alive at Day 5 without bronchospasms, unexpected infections, or a significant clinical deterioration compared to Baseline | 5 days | 
| Exploratory Endpoint: Proportion of patients with respiratory rate ≤ 23/min for 24 hours | Proportion of patients with respiratory rate ≤ 23/min for 24 hours | 5 days | 
| Exploratory endpoint: Change in respiratory rate from baseline to Day 5 | Change in respiratory rate from baseline to Day 5 | 5 days | 
| Exploratory endpoint: Proportion of patients with SpO2 saturation ≥94% for at least 24 hours | Proportion of patients with SpO2 saturation ≥94% for at least 24 hours | 5 days | 
| Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5 | Change in SpO2 saturation from baseline to Day 5 | 5 days | 
| Exploratory endpoint: Proportion of patients with no artificial ventilation after 5 days of treatment | Proportion of patients with no artificial ventilation after 5 days of treatment | 5 days | 
| Exploratory endpoint: Proportion of patients with a change in absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment | Proportion of patients with a change in the absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment | 7 days | 
| Exploratory endpoint: Change in the absolute lymphocyte count from baseline to Day 5 | Change in the absolute lymphocyte count from baseline to Day 5 | 5 days | 
| Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR), sustained for ≥48 hours after 5 days of treatment | Proportion of patients with a change in the neutrophil-to-lymphocyte ratio, sustained for ≥48 hours after 5 days of treatment | 7 days | 
| Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5 | Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5 | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, COVID-19, Exosomes, CD24, CD-24 exosomes