Clinical trial NCT04747574: Evaluation of the Safety of CD24-Exosomes in Patients With COVID-19 Infection
Official title: A Phase I Feasibility Study to Evaluate the Safety of CD24-Exosomes in Patients With Moderate/Severe COVID-19 Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: SARS-CoV-2
Keywords: SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
COVID-19
Exosomes
ARDS
CD24
CD-24 exosomes
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2021-02-10
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Primary safety endpoint: Adverse events
timeFrame: 35 days
Secondary outcomes:
measure: Exploratory Endpoint: Alive at Day 5 without bronchospasms, unexpected infections, or clinical deterioration
timeFrame: 5 days
measure: Exploratory Endpoint: Proportion of patients with respiratory rate ≤ 23/min for 24 hours
timeFrame: 5 days
measure: Exploratory endpoint: Change in respiratory rate from baseline to Day 5
timeFrame: 5 days
measure: Exploratory endpoint: Proportion of patients with SpO2 saturation ≥94% for at least 24 hours
timeFrame: 5 days
measure: Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5
timeFrame: 5 days
measure: Exploratory endpoint: Proportion of patients with no artificial ventilation after 5 days of treatment
timeFrame: 5 days
measure: Exploratory endpoint: Proportion of patients with a change in absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment
timeFrame: 7 days
measure: Exploratory endpoint: Change in the absolute lymphocyte count from baseline to Day 5
timeFrame: 5 days
measure: Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR), sustained for ≥48 hours after 5 days of treatment
timeFrame: 7 days
measure: Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5
timeFrame: 5 days
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Tel Aviv Medical Center
Study officials:
affiliation: Tel Aviv Medical Center
name: Nadir Arber, Prof.
role: PRINCIPAL_INVESTIGATOR
References: