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

• ClinicalTrials.gov Identifier: NCT04747574
• Recruitment Status: Recruiting
• First Posted: February 10, 2021
• Last Update Posted: March 4, 2021
• Sponsor: Tel-Aviv Sourasky Medical Center
• Information provided by (Responsible Party): Eli Sprecher, MD, Tel-Aviv Sourasky Medical Center

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.

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2	Drug: EXO-CD24	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Feasibility Study to Evaluate the Safety of CD24-Exosomes in Patients With Moderate/Severe COVID-19 Infection
• Actual Study Start Date: September 25, 2020
• Estimated Primary Completion Date: February 25, 2021
• Estimated Study Completion Date: March 25, 2021

Arms and Interventions

Arm

Intervention/treatment

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.

Outcome Measures

Primary Outcome Measures :

1. Primary safety endpoint: Adverse events [ Time Frame: 35 days ]
   Number of adverse events, and adverse events leading to premature study termination.

Secondary Outcome Measures :

1. Exploratory Endpoint: Alive at Day 5 without bronchospasms, unexpected infections, or clinical deterioration [ Time Frame: 5 days ]
   A composite endpoint comprised of alive at Day 5 without bronchospasms, unexpected infections, or a significant clinical deterioration compared to Baseline
2. Exploratory Endpoint: Proportion of patients with respiratory rate ≤ 23/min for 24 hours [ Time Frame: 5 days ]
   Proportion of patients with respiratory rate ≤ 23/min for 24 hours
3. Exploratory endpoint: Change in respiratory rate from baseline to Day 5 [ Time Frame: 5 days ]
   Change in respiratory rate from baseline to Day 5
4. Exploratory endpoint: Proportion of patients with SpO2 saturation ≥94% for at least 24 hours [ Time Frame: 5 days ]
   Proportion of patients with SpO2 saturation ≥94% for at least 24 hours
5. Exploratory endpoint: Change in SpO2 saturation from baseline to Day 5 [ Time Frame: 5 days ]
   Change in SpO2 saturation from baseline to Day 5
6. Exploratory endpoint: Proportion of patients with no artificial ventilation after 5 days of treatment [ Time Frame: 5 days ]
   Proportion of patients with no artificial ventilation after 5 days of treatment
7. Exploratory endpoint: Proportion of patients with a change in absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment [ Time Frame: 7 days ]
   Proportion of patients with a change in the absolute lymphocyte count, sustained for ≥48 hours after 5 days of treatment
8. Exploratory endpoint: Change in the absolute lymphocyte count from baseline to Day 5 [ Time Frame: 5 days ]
   Change in the absolute lymphocyte count from baseline to Day 5
9. Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR), sustained for ≥48 hours after 5 days of treatment [ Time Frame: 7 days ]
   Proportion of patients with a change in the neutrophil-to-lymphocyte ratio, sustained for ≥48 hours after 5 days of treatment
10. Exploratory endpoint: Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5 [ Time Frame: 5 days ]
    Change in neutrophil-to-lymphocyte ratio (NLR) from baseline to Day 5

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Nadir Arber, Prof. MD MHA; 972524266595 ext 0; nadira@tlvmc.gov.il

Locations

Israel

Tel Aviv Medical Center; Recruiting

Tel Aviv, Israel

Contact: Nadir Arber, Prof. nadira@tlvmc.gov.il

Sponsors and Collaborators

Tel-Aviv Sourasky Medical Center

Investigators

• Principal Investigator: Nadir Arber, Prof.; Tel Aviv Medical Center

More Information

• Responsible Party: Eli Sprecher, MD, Nadir Arber MD, MSc, MHA Professor of Medicine and Gastroenterology. Head of the Health Promotion Center and the Integrated Cancer Prevention Center Tel-Aviv Sourasky Medical Center, Tel-Aviv Sourasky Medical Center
• ClinicalTrials.gov Identifier: NCT04747574
• Other Study ID Numbers: 0254-20-TLV
• First Posted: February 10, 2021
• Last Update Posted: March 4, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eli Sprecher, MD, Tel-Aviv Sourasky Medical Center:

SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; COVID-19; Exosomes; ARDS; CD24; CD-24 exosomes

Additional relevant MeSH terms:

COVID-19; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases