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

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

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.

Study Overview

• Status: Recruiting
• Conditions: SARS-CoV-2
• Intervention / Treatment: Drug: EXO-CD24

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.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Nadir Arber, Prof. MD MHA; Phone Number: 972524266595; Email: nadira@tlvmc.gov.il

Study Locations

• Israel
  • Tel Aviv, Israel
    • Recruiting
    • Tel Aviv Medical Center
    • Contact: Nadir Arber, Prof.; Email: nadira@tlvmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: EXO-CD24 exosome treatment; 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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary safety endpoint: Adverse events	Number of adverse events, and adverse events leading to premature study termination.	35 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Exploratory endpoint: Change in respiratory rate from baseline to Day 5	Change in respiratory rate from baseline to Day 5	5 days
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
Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5	Change in SpO2 saturation from baseline to Day 5	5 days
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Investigators: Principal Investigator: Nadir Arber, Prof., Tel Aviv Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2020
• Primary Completion (Anticipated): February 25, 2021
• Study Completion (Anticipated): March 25, 2021

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 4, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; ARDS; Severe acute respiratory syndrome coronavirus 2; Exosomes; CD24; CD-24 exosomes
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 0254-20-TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No