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

SARS-CoV-2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04747574
• Other study ID #: 0254-20-TLV
• Status: Recruiting
• Phase: Phase 1
• Start date: September 25, 2020
• Est. completion date: March 25, 2021

Study information

• Verified date: March 2021
• Source: Tel-Aviv Sourasky Medical Center
• Contact: Nadir Arber, Prof. MD MHA
• Phone: 972524266595
• Email: nadira[@]tlvmc.gov.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: March 25, 2021
• Est. primary completion date: February 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Infection
• SARS-CoV-2

Intervention

Drug:
• EXO-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.

Locations

Country	Name	City	State
Israel	Tel Aviv Medical Center	Tel Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Tel-Aviv Sourasky Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary safety endpoint: Adverse events	Number of adverse events, and adverse events leading to premature study termination.	35 days
Secondary	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
Secondary	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
Secondary	Exploratory endpoint: Change in respiratory rate from baseline to Day 5	Change in respiratory rate from baseline to Day 5	5 days
Secondary	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
Secondary	Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5	Change in SpO2 saturation from baseline to Day 5	5 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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