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

Tel Aviv Sourasky Medical Center

Status and phase: Unknown; Phase 1

Conditions: SARS-CoV-2

Treatments: Drug: EXO-CD24

Study type: Interventional

Funder types: Other

Identifiers

NCT04747574

0254-20-TLV

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

EXO-CD24 exosome treatment

Other group

Description:

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.

Treatment:

Drug: EXO-CD24