SARS-CoV-2
Conditions
Keywords
SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, COVID-19, Exosomes, ARDS, CD24, CD-24 exosomes
Brief summary
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
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.
Interventions
DRUGEXO-CD24
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.
Sponsors
Tel-Aviv Sourasky Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. A COVID-19 diagnosis confirmed with a SARS-CoV-2 viral infection positive polymerase chain reaction (PCR) test 2. Disease severity: Moderate/severe according to the following criteria (at least one clinical parameter and one laboratory parameter are required): 1. 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 2. 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 3. Willing and able to sign an informed consent
Exclusion criteria
1. Age\<18 years or \>85 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. Unwilling or unable to provide informed consent 6. Participation in any other study in the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary safety endpoint: Adverse events | 35 days | Number of adverse events, and adverse events leading to premature study termination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Endpoint: Proportion of patients with respiratory rate ≤ 23/min for 24 hours | 5 days | Proportion of patients with respiratory rate ≤ 23/min for 24 hours |
| Exploratory endpoint: Change in respiratory rate from baseline to Day 5 | 5 days | Change in respiratory rate from baseline to Day 5 |
| Exploratory endpoint: Proportion of patients with SpO2 saturation ≥94% for at least 24 hours | 5 days | Proportion of patients with SpO2 saturation ≥94% for at least 24 hours |
| Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5 | 5 days | Change in SpO2 saturation from baseline to Day 5 |
| Exploratory Endpoint: Alive at Day 5 without bronchospasms, unexpected infections, or clinical deterioration | 5 days | A composite endpoint comprised of alive at Day 5 without bronchospasms, unexpected infections, or a significant clinical deterioration compared to Baseline |
| Exploratory endpoint: Proportion of patients with a change in absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment | 7 days | Proportion of patients with a change in the absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment |
| Exploratory endpoint: Change in the absolute lymphocyte count from baseline to Day 5 | 5 days | Change in the absolute lymphocyte count from baseline to Day 5 |
| Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR), sustained for ≥48 hours after 5 days of treatment | 7 days | Proportion of patients with a change in the neutrophil-to-lymphocyte ratio, sustained for ≥48 hours after 5 days of treatment |
| Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5 | 5 days | Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5 |
| Exploratory endpoint: Proportion of patients with no artificial ventilation after 5 days of treatment | 5 days | Proportion of patients with no artificial ventilation after 5 days of treatment |
Countries
Israel
Contacts
Primary ContactNadir Arber, Prof. MD MHA
Outcome results
None listed