search
Back to results

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

Primary Purpose

SARS-CoV-2

Status
Unknown status
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
EXO-CD24
Sponsored by
Tel-Aviv Sourasky Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for SARS-CoV-2 focused on measuring SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, COVID-19, Exosomes, ARDS, CD24, CD-24 exosomes

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  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

Sites / Locations

  • Tel Aviv Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

EXO-CD24 exosome treatment

Arm 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.

Outcomes

Primary Outcome Measures

Primary safety endpoint: Adverse events
Number of adverse events, and adverse events leading to premature study termination.

Secondary Outcome Measures

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
Exploratory Endpoint: Proportion of patients with respiratory rate ≤ 23/min for 24 hours
Proportion of patients with respiratory rate ≤ 23/min for 24 hours
Exploratory endpoint: Change in respiratory rate from baseline to Day 5
Change in respiratory rate from baseline to Day 5
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
Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5
Change in SpO2 saturation from baseline to Day 5
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
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
Exploratory endpoint: Change in the absolute lymphocyte count from baseline to Day 5
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
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
Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5

Full Information

First Posted
January 26, 2021
Last Updated
March 2, 2021
Sponsor
Tel-Aviv Sourasky Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT04747574
Brief Title
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

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
September 25, 2020 (Actual)
Primary Completion Date
February 25, 2021 (Anticipated)
Study Completion Date
March 25, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tel-Aviv Sourasky Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2
Keywords
SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, COVID-19, Exosomes, ARDS, CD24, CD-24 exosomes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EXO-CD24 exosome treatment
Arm Type
Other
Arm 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.
Intervention Type
Drug
Intervention Name(s)
EXO-CD24
Intervention Description
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.
Primary Outcome Measure Information:
Title
Primary safety endpoint: Adverse events
Description
Number of adverse events, and adverse events leading to premature study termination.
Time Frame
35 days
Secondary Outcome Measure Information:
Title
Exploratory Endpoint: Alive at Day 5 without bronchospasms, unexpected infections, or clinical deterioration
Description
A composite endpoint comprised of alive at Day 5 without bronchospasms, unexpected infections, or a significant clinical deterioration compared to Baseline
Time Frame
5 days
Title
Exploratory Endpoint: Proportion of patients with respiratory rate ≤ 23/min for 24 hours
Description
Proportion of patients with respiratory rate ≤ 23/min for 24 hours
Time Frame
5 days
Title
Exploratory endpoint: Change in respiratory rate from baseline to Day 5
Description
Change in respiratory rate from baseline to Day 5
Time Frame
5 days
Title
Exploratory endpoint: Proportion of patients with SpO2 saturation ≥94% for at least 24 hours
Description
Proportion of patients with SpO2 saturation ≥94% for at least 24 hours
Time Frame
5 days
Title
Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5
Description
Change in SpO2 saturation from baseline to Day 5
Time Frame
5 days
Title
Exploratory endpoint: Proportion of patients with no artificial ventilation after 5 days of treatment
Description
Proportion of patients with no artificial ventilation after 5 days of treatment
Time Frame
5 days
Title
Exploratory endpoint: Proportion of patients with a change in absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment
Description
Proportion of patients with a change in the absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment
Time Frame
7 days
Title
Exploratory endpoint: Change in the absolute lymphocyte count from baseline to Day 5
Description
Change in the absolute lymphocyte count from baseline to Day 5
Time Frame
5 days
Title
Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR), sustained for ≥48 hours after 5 days of treatment
Description
Proportion of patients with a change in the neutrophil-to-lymphocyte ratio, sustained for ≥48 hours after 5 days of treatment
Time Frame
7 days
Title
Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5
Description
Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5
Time Frame
5 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nadir Arber, Prof. MD MHA
Phone
972524266595
Ext
0
Email
nadira@tlvmc.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nadir Arber, Prof.
Organizational Affiliation
Tel Aviv Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tel Aviv Medical Center
City
Tel Aviv
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadir Arber, Prof.
Email
nadira@tlvmc.gov.il

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs