A Phase II Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Exosomes Overexpressing CD24 to Prevent Clinical Deterioration in Patients With Moderate or Severe COVID-19 Infection

Phase 2

• Conditions: COVID-19 Disease
• Interventions: Drug: Exosomes overexpressing CD24

• Registration Number: NCT04969172
• Lead Sponsor: Eli Sprecher, MD

Brief Summary

A Phase II Randomized, double-blind, Placebo-controlled Study to Evaluate the safety and efficacy of exosomes overexpressing CD24 to prevent clinical deterioration .The study population will include patients with moderate or severe COVID-19 infection and laboratory markers predictive of the cytokine storm from the Corona department of each site, who have provided an informed consent.

155 patients will be randomized in a 2:1 ratio to receive either 1010 exosome particles (103 patients) or placebo (52 patients).The exosomes will be diluted in 4ml normal saline for inhalation, administered once daily (QD) for 5 days.

Placebo (saline) will be prepared for inhalation and administered in the same manner as the exosomes.

Detailed Description

The exosomes will be diluted in 4ml normal saline for inhalation, administered once daily (QD) for 5 days.

Placebo (saline) will be prepared for inhalation and administered in the same manner as the exosomes.

Study treatments will be given as add-on to standard of care. Following the 5 days of treatment, patients will remain in follow-up for 23 additional days. Patients who will be discharged before the end of the 5-day treatment period will continue to receive treatment at home. Treatment administration and the study assessments will be carried out by the research personnel at the home of the patient, implementing the required protective measures.

On Day 28, when the isolation period is completed, these patients will arrive at the study site for the follow-up visit.

Study Timeline

• Status Verified: 2021-07
• Study Start: 2021-07-11
• Study First Submitted: 2021-07-18
• Study First Submitted QC: 2021-07-18
• Last Update Submitted: 2021-07-18
• Study First Posted: 2021-07-20
• Last Update Posted: 2021-07-20
• Primary Completion: 2022-07-11
• Study Completion: 2022-07-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

1. A COVID-19 diagnosis confirmed with a SARS-coV-2 viral infection positive polymerase chain reaction (PCR) test

2. Age 18-80 years

3. Severity of disease according to the following criteria (at least one clinical parameter and one laboratory parameter are required):

   a. Clinical and Imaging-based evaluation i. Respiratory rate > 23/min and < 30/min ii. SpO2 at room air ≤94% and ≥90% iii. Bilateral pulmonary infiltrates >50% within 24-48 hours or a severe deterioration compared to imaging at admission b. Evidence of an exacerbated inflammatory process i. LDH score> 450 U/L ii. CRP >50 mg/L iii. Ferritin >1650 ng/ml iv. Lymphocytes >800 cells/mm3 v. D-dimers >1 mcg/ml

4. Willing and able to sign an informed consent

Exclusion Criteria

1. Age<18 years or >80 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. Patients with Immunodeficiency (eg, CLL, HIV, rituximab therapy)
6. Unwilling or unable to provide informed consent
7. Participation in any other Interventional study in the last 30 days

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1010 Exosome	Exosomes overexpressing CD24	103 patients will receive either 1010 exosome particles.
Placebo	Exosomes overexpressing CD24	52 patients will receive placebo- saline.

Primary Outcome Measures

Name	Time	Method
To evaluate respiratory failure (defined as the need for mechanical ventilation, ECMO, non-invasive ventilation, or high-flow oxygen devices) rate.	One year
To evaluate the death rate.	One year
To evaluate the safety of EXO-CD24 in the treatment of patients with moderate or severe COVID-19 disease	One year
To assess the efficacy of EXO-CD24 in the clinical improvement of COVID-19 disease	One year
To evaluate time to improvement and recovery (COVID-19 clinical severity score of 3 or lower).	One year
To evaluate time from hospitalization to hospital discharge.	One year
To assess the COVID-19-related symptoms using patient-reported outcome measure (PRO) score.	One year

Secondary Outcome Measures

Name	Time	Method
To evaluate the effect of EXO-CD24 on the change in blood oxygen saturation (SpO2).	One year
To evaluate the effect of EXO-CD24 on the respiratory rate.	One year
To evaluate the effect of EXO-CD24 on the level of inflammatory markers (eg, CRP, ferritin, fibrinogen, di-dimers, IL-6, LDH, lymphocytes count.	One year
To evaluate the effect of EXO-CD24 on the proportion of patients requiring ventilation.	One year

Trial Locations

Locations (1)

Tel-Aviv Sourasky Medical Center; 🇮🇱 Tel-Aviv, Israel