Clinical trial NCT04969172: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19 Disease
Keywords: AE- Adverse event
BUN - Blood urea nitrogen
CI- Confidence Interval
CMP - Clinical monitoring plan
CONSORT- Consolidated Standards of Reporting Trials
CRF - Case Report Form
DAMP- Damage-associated molecular patterns
DMEM- Dulbecco's Modified Eagle's Medium
GCP - Good Clinical Practice
GMP- Good Manufacturing Practice
GVHD- Graft-versus-host disease
HCT - Hematopoietic stem cell transplantation
ICH- International Conference on Harmonization
IDSA- Infectious Diseases Society of America
IRB- Institutional Review Board
ITT- Intend-to-Treat analysis set
mITT- Modified Intent-to-Treat analysis set
NLR - Neutrophil-to-lymphocyte ratio
PCR - Polymerase chain reaction
PI- Principal Investigator
PP- Per-Protocol analysis set
SA- Safety analysis set
SAE- Serious adverse event
SoA- Schedule of Activities
TLR- Toll-like receptors
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: OBCTCD24 Ltd
First posted: 2021-07-20
Enrollment: 155
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: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the safety of EXO-CD24 in the treatment of patients with moderate or severe COVID-19 disease
timeFrame: One year
measure: To assess the efficacy of EXO-CD24 in the clinical improvement of COVID-19 disease
timeFrame: One year
measure: To evaluate respiratory failure (defined as the need for mechanical ventilation, ECMO, non-invasive ventilation, or high-flow oxygen devices) rate.
timeFrame: One year
measure: To evaluate the death rate.
timeFrame: One year
measure: To evaluate time to improvement and recovery (COVID-19 clinical severity score of 3 or lower).
timeFrame: One year
measure: To evaluate time from hospitalization to hospital discharge.
timeFrame: One year
measure: To assess the COVID-19-related symptoms using patient-reported outcome measure (PRO) score.
timeFrame: One year
Secondary outcomes:
measure: To evaluate the effect of EXO-CD24 on the respiratory rate.
timeFrame: One year
measure: To evaluate the effect of EXO-CD24 on the change in blood oxygen saturation (SpO2).
timeFrame: One year
measure: To evaluate the effect of EXO-CD24 on the proportion of patients requiring ventilation.
timeFrame: One year
measure: To evaluate the effect of EXO-CD24 on the level of inflammatory markers (eg, CRP, ferritin, fibrinogen, di-dimers, IL-6, LDH, lymphocytes count.
timeFrame: One year
Other outcomes:
Locations:
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
Study officials:
References: