Back to resultsSafety and Efficacy of Exosomes Overexpressing CD24 in Two Doses for Patients With Moderate or Severe COVID-19
Primary Purpose
Covid19
Status
Unknown status
Phase
Phase 2
Locations
Greece
Study Type
Interventional
Intervention
CovenD24
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria:
- A COVID-19 diagnosis confirmed with a SARS-CoV-2 infection positive polymerase chain reaction (PCR) within 30 days of screening.
- Age 18-80 years.
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
- Willing and able to sign an informed consent.
Exclusion Criteria:
- Any concomitant illness that, based on the judgment of the Investigator might affect the interpretation or the results of the study (i.e., immunodeficiency).
- 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.
- Previous complete or partial vaccination for SARS-CoV-2.
- Pregnancy [positive urine pregnancy test (women of childbearing potential only)] or breastfeeding.
- Participation in any other Interventional study in the last 30 days
- Active cancer.
Sites / Locations
- 3rd Department of Medicine, "Sotiria" Thoracic Diseases General Hospital of Athens
- Attikon University HospitalRecruiting
- 7th Respiratory Medicine Department, "Sotiria" Thoracic Diseases General Hospital of Athens
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
10^9 dose of exosomes overexpressing CD24
10^10 dose of exosomes overexpressing CD24
Arm Description
The patients will receive the dose of 10^9 exosomes overexpressing CD24
The patients will receive the dose of 10^10 exosomes overexpressing CD24
Outcomes
Primary Outcome Measures
Collection of serious adverse events
Incidence of treatment (dose)-related serious adverse events.
Incidence of all adverse events related or unrelated to the study treatment.
Proportion of patients related with Respiratory rate and SpO2 saturation
Proportion of patients with respiratory rate < 23/min for at least 24 hours, on Day 7.
Proportion of patients with SpO2 saturation >94%, on room air for at least 24 hours, on Day 7.
Proportion of patients with a decrease by 50% in either CRP/LDH/Fibrinogen/Ferritin/D-dimers from baseline to Day 7.
Secondary Outcome Measures
Improvement of COVID19 status from severe to moderate
• Rate of categorical and absolute score improvement of COVID-19 status on Day 7 improving from "Severe" to at least "Moderate" or from "Moderate" to "Moderate-Mild"
Time to recovery
• Time to recovery, measured from enrolment (Day 1) to recovery or last follow-up (Day 28).
Death rate
• Death rate at end of study (Day 28)
No need for mechanical ventilation
• Proportion of patients with no mechanical ventilation (ECMO, NIV, high flow) on Day 7.
Patients status regarding haemodynamic instability
• Proportion of patients with haemodynamic instability or requiring vasopressors on Day 7.
Oxygen saturation
• Change in the SpO2/FiO2 ratio on Day 7.
Time to death or respiratory failure
• Time to death or respiratory failure (defined as an arterial oxygen pressure (PaO2) of <60 mmHg and/or an arterial carbon dioxide pressure (PaCO2) of >45 mmHg, or the need for mechanical ventilation, ECMO, non-invasive ventilation, or high-flow oxygen devices) within 28 days of the study period (Day 1 to Day 28).
Hospital discharge time
• Hospital discharge time within 28 days of the study period, calculated from the day of randomization (Day 1) to discharge or last follow-up (Day 28), whichever comes first.
No of patients that will need Intensive Care Unit
• Proportion of patients requiring admission to an Intensive-Care Unit (ICU) on Day 7.
No of patients with respiratory rate < 23/min
• Proportion of patients with respiratory rate < 23/min for 24 hours at every visit until Day 28, inclusive.
No of patients with change in respiratory change
• Proportion of patients with change [decrease/no change (±2 breaths/min)/improvement] in respiratory rate from baseline to Day 7.
No of patients with SpO2 >94%
• Proportion of patients with SpO2 >94% on room air, for at least 24 hours at every visit until Day 28, inclusive.
No of patients with change in oxygen saturation
• Proportion of patients with change [decrease/no change (±2 %)/improvement] in SpO2 saturation from baseline to Day 7.
No of patients with change in lymphocyte count
• Proportion of patients with an increase of 25% in the absolute lymphocyte count, sustained for ≥24 hours on Day 7.
Changes in absolute lymphocyte count
• Change in absolute lymphocyte count from baseline to Day 7.
No of patients with changes in the neutrophil-to-lymphocyte ratio
• Proportion of patients with a decrease of 20% in the neutrophil-to-lymphocyte ratio (NLR), sustained for ≥24 hours on Day 7.
Changes in the neutrophil-to-lymphocyte ratio
• Change in NLR from baseline to Day 7.
No of patients with changes in disease severity
• Percentage of patients within each severity rating on the ordinal scale within 28 days of the study period (Day 1 to Day 28).
Time of disease improvement
• Time to improvement in the categorical and ordinal scale, measured from randomization (Day 1) to last study follow-up (Day 28).
Changes in COVID-19 clinical severity
• Change in the COVID-19 clinical severity from baseline [before-treatment assessment (Screening/Day 1)] up to Day 28.
Changes in common COVID-19 related symptoms
• Change from baseline of 14 Common COVID-19-Related Symptoms, as assessed through an Investigator interview.
Changes in supplemental oxygen over time
• Change in the flow rate of supplemental oxygen administration over time.
Duration of oxygen administration
• The duration of supplemental (non-invasive) oxygen administration.
Full Information
NCT ID
NCT04902183
First Posted
May 21, 2021
Last Updated
June 12, 2021
Sponsor
Athens Medical Society
Collaborators
OBCTCD24 Ltd, Elpen Pharmaceutical Co. Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04902183
Brief Title
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
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 9, 2021 (Actual)
Primary Completion Date
September 1, 2021 (Anticipated)
Study Completion Date
September 1, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Athens Medical Society
Collaborators
OBCTCD24 Ltd, Elpen Pharmaceutical Co. Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
Masking
Participant
Masking Description
The administrated dose will be unknown to the patients
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
10^9 dose of exosomes overexpressing CD24
Arm Type
Experimental
Arm Description
The patients will receive the dose of 10^9 exosomes overexpressing CD24
Arm Title
10^10 dose of exosomes overexpressing CD24
Arm Type
Experimental
Arm Description
The patients will receive the dose of 10^10 exosomes overexpressing CD24
Intervention Type
Drug
Intervention Name(s)
CovenD24
Other Intervention Name(s)
Exo-CD24
Intervention Description
The drug will be administrated once daily for 5 days
Primary Outcome Measure Information:
Title
Collection of serious adverse events
Description
Incidence of treatment (dose)-related serious adverse events.
Incidence of all adverse events related or unrelated to the study treatment.
Time Frame
Through study completion, an average of 4 months
Title
Proportion of patients related with Respiratory rate and SpO2 saturation
Description
Proportion of patients with respiratory rate < 23/min for at least 24 hours, on Day 7.
Proportion of patients with SpO2 saturation >94%, on room air for at least 24 hours, on Day 7.
Proportion of patients with a decrease by 50% in either CRP/LDH/Fibrinogen/Ferritin/D-dimers from baseline to Day 7.
Time Frame
Through study completion, an average of 4 months
Secondary Outcome Measure Information:
Title
Improvement of COVID19 status from severe to moderate
Description
• Rate of categorical and absolute score improvement of COVID-19 status on Day 7 improving from "Severe" to at least "Moderate" or from "Moderate" to "Moderate-Mild"
Time Frame
Through study completion, an average of 4 months
Title
Time to recovery
Description
• Time to recovery, measured from enrolment (Day 1) to recovery or last follow-up (Day 28).
Time Frame
Through study completion, an average of 4 months
Title
Death rate
Description
• Death rate at end of study (Day 28)
Time Frame
Through study completion, an average of 4 months
Title
No need for mechanical ventilation
Description
• Proportion of patients with no mechanical ventilation (ECMO, NIV, high flow) on Day 7.
Time Frame
Through study completion, an average of 4 months
Title
Patients status regarding haemodynamic instability
Description
• Proportion of patients with haemodynamic instability or requiring vasopressors on Day 7.
Time Frame
Through study completion, an average of 4 months
Title
Oxygen saturation
Description
• Change in the SpO2/FiO2 ratio on Day 7.
Time Frame
Through study completion, an average of 4 months
Title
Time to death or respiratory failure
Description
• Time to death or respiratory failure (defined as an arterial oxygen pressure (PaO2) of <60 mmHg and/or an arterial carbon dioxide pressure (PaCO2) of >45 mmHg, or the need for mechanical ventilation, ECMO, non-invasive ventilation, or high-flow oxygen devices) within 28 days of the study period (Day 1 to Day 28).
Time Frame
Through study completion, an average of 4 months
Title
Hospital discharge time
Description
• Hospital discharge time within 28 days of the study period, calculated from the day of randomization (Day 1) to discharge or last follow-up (Day 28), whichever comes first.
Time Frame
Through study completion, an average of 4 months
Title
No of patients that will need Intensive Care Unit
Description
• Proportion of patients requiring admission to an Intensive-Care Unit (ICU) on Day 7.
Time Frame
Through study completion, an average of 4 months
Title
No of patients with respiratory rate < 23/min
Description
• Proportion of patients with respiratory rate < 23/min for 24 hours at every visit until Day 28, inclusive.
Time Frame
Through study completion, an average of 4 months
Title
No of patients with change in respiratory change
Description
• Proportion of patients with change [decrease/no change (±2 breaths/min)/improvement] in respiratory rate from baseline to Day 7.
Time Frame
Through study completion, an average of 4 months
Title
No of patients with SpO2 >94%
Description
• Proportion of patients with SpO2 >94% on room air, for at least 24 hours at every visit until Day 28, inclusive.
Time Frame
Through study completion, an average of 4 months
Title
No of patients with change in oxygen saturation
Description
• Proportion of patients with change [decrease/no change (±2 %)/improvement] in SpO2 saturation from baseline to Day 7.
Time Frame
Through study completion, an average of 4 months
Title
No of patients with change in lymphocyte count
Description
• Proportion of patients with an increase of 25% in the absolute lymphocyte count, sustained for ≥24 hours on Day 7.
Time Frame
Through study completion, an average of 4 months
Title
Changes in absolute lymphocyte count
Description
• Change in absolute lymphocyte count from baseline to Day 7.
Time Frame
Through study completion, an average of 4 months
Title
No of patients with changes in the neutrophil-to-lymphocyte ratio
Description
• Proportion of patients with a decrease of 20% in the neutrophil-to-lymphocyte ratio (NLR), sustained for ≥24 hours on Day 7.
Time Frame
Through study completion, an average of 4 months
Title
Changes in the neutrophil-to-lymphocyte ratio
Description
• Change in NLR from baseline to Day 7.
Time Frame
Through study completion, an average of 4 months
Title
No of patients with changes in disease severity
Description
• Percentage of patients within each severity rating on the ordinal scale within 28 days of the study period (Day 1 to Day 28).
Time Frame
Through study completion, an average of 4 months
Title
Time of disease improvement
Description
• Time to improvement in the categorical and ordinal scale, measured from randomization (Day 1) to last study follow-up (Day 28).
Time Frame
Through study completion, an average of 4 months
Title
Changes in COVID-19 clinical severity
Description
• Change in the COVID-19 clinical severity from baseline [before-treatment assessment (Screening/Day 1)] up to Day 28.
Time Frame
Through study completion, an average of 4 months
Title
Changes in common COVID-19 related symptoms
Description
• Change from baseline of 14 Common COVID-19-Related Symptoms, as assessed through an Investigator interview.
Time Frame
Through study completion, an average of 4 months
Title
Changes in supplemental oxygen over time
Description
• Change in the flow rate of supplemental oxygen administration over time.
Time Frame
Through study completion, an average of 4 months
Title
Duration of oxygen administration
Description
• The duration of supplemental (non-invasive) oxygen administration.
Time Frame
Through study completion, an average of 4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A COVID-19 diagnosis confirmed with a SARS-CoV-2 infection positive polymerase chain reaction (PCR) within 30 days of screening.
Age 18-80 years.
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
Willing and able to sign an informed consent.
Exclusion Criteria:
Any concomitant illness that, based on the judgment of the Investigator might affect the interpretation or the results of the study (i.e., immunodeficiency).
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.
Previous complete or partial vaccination for SARS-CoV-2.
Pregnancy [positive urine pregnancy test (women of childbearing potential only)] or breastfeeding.
Participation in any other Interventional study in the last 30 days
Active cancer.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sotirios Tsiodras, Prof
Phone
0030-210-5831990
Email
stsiodras.office@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Nadir Arber, Prof
Email
nadira@tlvmc.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sotirios Tsiodras, Prof
Organizational Affiliation
Attikon University Hospital, Athens, Greece
Official's Role
Principal Investigator
Facility Information:
Facility Name
3rd Department of Medicine, "Sotiria" Thoracic Diseases General Hospital of Athens
City
Athens
State/Province
Attica
ZIP/Postal Code
11527
Country
Greece
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Garyfallia Poulakou, Ass. Prof
Phone
0030-210-7763439
Facility Name
Attikon University Hospital
City
Athens
State/Province
Attica
ZIP/Postal Code
12462
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sotirios Tsiodras, Prof
Phone
210-5831990
Email
stsiodras.office@gmail.com
Facility Name
7th Respiratory Medicine Department, "Sotiria" Thoracic Diseases General Hospital of Athens
City
Athens
State/Province
Attika
ZIP/Postal Code
11527
Country
Greece
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mina Gaga, Director
Phone
0030-210-7781720
Email
7th_klin@otenet.gr
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of Exosomes Overexpressing CD24 in Two Doses for Patients With Moderate or Severe COVID-19
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