Clinical trial NCT04902183: Safety and Efficacy of Exosomes Overexpressing CD24 in Two Doses for Patients With Moderate or Severe COVID-19
Official title: A Phase II Randomized, Single-blind Dose Study to Evaluate the Safety and Efficacy of Exosomes Overexpressing CD24 in 10^9 Dose Versus 10^10 Dose, for the Prevention of Clinical Deterioration in Patients With Moderate or Severe COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid19
Lead sponsor: Athens Medical Society
Sponsor class: OTHER
Collaborators: name: OBCTCD24 Ltd
name: Elpen Pharmaceutical Co. Inc.
First posted: 2021-05-26
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a two arms study; one arm will receive 10\^9 dose and the second arm will receive 10\^10 dose of exosomes overexpressing CD24
Primary purpose: TREATMENT

Brief summary: This is a phase II randomized, single-blind dose study to evaluate the safety and efficacy of exosomes overexpressing CD24 of two doses, Dose 1 - 10\^9 exosome particles (per dose) versus Dose 2 - 10\^10 exosome particles (per dose), to prevent clinical deterioration in patients with Moderate or Severe COVID-19 infection.

Detailed description: The study population will include patients with moderate or severe COVID-19 and laboratory markers predictive of the cytokine storm, who have provided an informed consent.

90 patients will be randomized in a 1:1 ratio to receive either 109 exosome particles (45 patients) or 1010 exosome particles (45 patients).

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

Study treatments will be given as an add-on to the standard of care. Following the 5 days of treatment, patients will remain in follow-up for 23 additional days. In case of hospital discharge before the full follow-up planned, the patient will be required to return to the site for completion of all study assessments.

Eligibility criteria: Inclusion Criteria:

1. A COVID-19 diagnosis confirmed with a SARS-CoV-2 infection positive polymerase chain reaction (PCR) within 30 days of screening.
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 \>25% within 24-48 hours or a severe deterioration compared to imaging at admission.

   b. Evidence of an exacerbated inflammatory process i. LDH \> 300 U/L or what is the upper limit for normal per age ii. CRP \>25 mg/L iii. Ferritin \>500 ng/ml iv. Lymphocytes \<800 cells/mm3 v. D-dimers \> 500ng/ml
4. Willing and able to sign an informed consent.

Exclusion Criteria:

1. Any concomitant illness that, based on the judgment of the Investigator might affect the interpretation or the results of the study (i.e., immunodeficiency).
2. Mechanically-ventilated patient or patient who will probably require ICU admission or mechanical ventilation within 24 hours from enrolment, according to the Investigator's judgment.
3. Previous complete or partial vaccination for SARS-CoV-2.
4. Pregnancy \[positive urine pregnancy test (women of childbearing potential only)\] or breastfeeding.
5. Participation in any other Interventional study in the last 30 days
6. Active cancer.

Primary outcomes:
measure: Collection of serious adverse events
timeFrame: Through study completion, an average of 4 months
measure: Proportion of patients related with Respiratory rate and SpO2 saturation
timeFrame: Through study completion, an average of 4 months
Secondary outcomes:
measure: Improvement of COVID19 status from severe to moderate
timeFrame: Through study completion, an average of 4 months
measure: Time to recovery
timeFrame: Through study completion, an average of 4 months
measure: Death rate
timeFrame: Through study completion, an average of 4 months
measure: No need for mechanical ventilation
timeFrame: Through study completion, an average of 4 months
measure: Patients status regarding haemodynamic instability
timeFrame: Through study completion, an average of 4 months
measure: Oxygen saturation
timeFrame: Through study completion, an average of 4 months
measure: Time to death or respiratory failure
timeFrame: Through study completion, an average of 4 months
measure: Hospital discharge time
timeFrame: Through study completion, an average of 4 months
measure: No of patients that will need Intensive Care Unit
timeFrame: Through study completion, an average of 4 months
measure: No of patients with respiratory rate < 23/min
timeFrame: Through study completion, an average of 4 months
measure: No of patients with change in respiratory change
timeFrame: Through study completion, an average of 4 months
measure: No of patients with SpO2 >94%
timeFrame: Through study completion, an average of 4 months
measure: No of patients with change in oxygen saturation
timeFrame: Through study completion, an average of 4 months
measure: No of patients with change in lymphocyte count
timeFrame: Through study completion, an average of 4 months
measure: Changes in absolute lymphocyte count
timeFrame: Through study completion, an average of 4 months
measure: No of patients with changes in the neutrophil-to-lymphocyte ratio
timeFrame: Through study completion, an average of 4 months
measure: Changes in the neutrophil-to-lymphocyte ratio
timeFrame: Through study completion, an average of 4 months
measure: No of patients with changes in disease severity
timeFrame: Through study completion, an average of 4 months
measure: Time of disease improvement
timeFrame: Through study completion, an average of 4 months
measure: Changes in COVID-19 clinical severity
timeFrame: Through study completion, an average of 4 months
measure: Changes in common COVID-19 related symptoms
timeFrame: Through study completion, an average of 4 months
measure: Changes in supplemental oxygen over time
timeFrame: Through study completion, an average of 4 months
measure: Duration of oxygen administration
timeFrame: Through study completion, an average of 4 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 3rd Department of Medicine, "Sotiria" Thoracic Diseases General Hospital of Athens
state: Attica
city: Athens
country: Greece
facility: Attikon University Hospital
state: Attica
city: Athens
country: Greece
facility: 7th Respiratory Medicine Department, "Sotiria" Thoracic Diseases General Hospital of Athens
state: Attika
Study officials:
affiliation: Attikon University Hospital, Athens, Greece
name: Sotirios Tsiodras, Prof
role: PRINCIPAL_INVESTIGATOR
References: