NCT04493242|CompletedPhase 2ResultsDMCFDA Drug

Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS

EXIT-COVID19

Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS): A Phase II Clinical Trial

Direct Biologics, LLC ClinicalTrials.gov

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1 other identifier

DB-EF-PHASEII-001

Study Type

interventional

Target

102

Locations

1 country

Sites

Timeline

RegisteredJul 2020

StartedSep 2020

CompletionMay 2021

Brief Summary

To evaluate the safety and efficacy of intravenous administration of bone marrow derived extracellular vesicles, ExoFlo, versus placebo as treatment for moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) in patients with severe COVID-19.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

102

participants targeted

Target at P50-P75 for phase_2 covid19

Timeline

Completed

Started Sep 2020

Geographic Reach

1 country

6 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

8 months study duration

First Submitted

Initial submission to the registry

July 29, 2020

Completed

1 day until next milestone

First Posted

Study publicly available on registry

July 30, 2020

Completed

2 months until next milestone

Study Start

First participant enrolled

September 24, 2020

Completed

7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2021

Completed

21 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 22, 2021

Completed

1.9 years until next milestone

Results Posted

Study results publicly available

April 11, 2023

Completed

Last Updated

February 13, 2024

Status Verified

February 1, 2024

Enrollment Period

7 months

First QC Date

July 29, 2020

Results QC Date

February 13, 2023

Last Update Submit

February 9, 2024

Conditions

COVID-19 ARDS

Keywords

COVID-19ARDSExtracellular VesiclesExosome

Outcome Measures

Primary Outcomes (1)

Evaluation of 60-day Mortality Rate
To evaluate the 60-day mortality rate for IP 15mL as a treatment for COVID-19 associated moderate to severe ARDS compared to placebo. Reducing the mortality rate for hospitalized patients with COVID-19 associated ARDS is a measure of the treatment effect.
60 days

Secondary Outcomes (5)

Overall Survival Rates
Days 15, 30, 60
Proportion of Discharged Patients
Days 7, 30, 60
Time to Discharge
Number of days from the date of randomization until documented discharge from hospital, up to 60 days.
Incidence of Treatment Emergent Serious Adverse Events
61 days
Ventilation Free Days
Within 60 days of follow-up

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Normal saline 100 mL

Other: Intravenous normal saline

Experimental Dose 1

EXPERIMENTAL

Normal saline 90 mL and ExoFlo 10 mL

Biological: ExoFlo

Experimental Dose 2

EXPERIMENTAL

Normal saline 85 mL and ExoFlo 15 mL

Biological: ExoFlo

Interventions

ExoFloBIOLOGICAL

Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

Experimental Dose 1Experimental Dose 2

Intravenous normal salineOTHER

Placebo

Eligibility Criteria

Age18 Years - 85 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 18-85.
COVID-19 positive as defined by positive Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) SARS-CoV-2.
Moderate to severe ARDS as defined by modified Berlin definition, \* which includes timing within 1 week of known clinical insult or new or worsening respiratory symptoms; bilateral opacities not fully explained by effusions, or lung collapse; respiratory failure not fully explained by cardiac failure or fluid overload; PaO2/FiO2 ≤ 200 mm Hg.
\*Modified Berlin definition used in this study is the full Berlin definition, albeit without the PEEP specification, which implies mechanical ventilation.
Hypoxia requiring noninvasive oxygen support such as Nasal Cannula (NC), Nonrebreather (NRB), Bilevel Positive Airway Pressure (BIPAP), Continuous Positive Airway Pressure (CPAP), high flow nasal cannula oxygen (HFNC O2) or mechanical ventilation (MV) despite initiating standard of care.
If the candidate is either a male or female of reproductive potential, he or she must agree to use of double barrier method of highly effective birth control contraception such as condoms with oral contraceptive pill or choose to remain abstinent if already practicing abstinence during the screening period. The required duration of usage of double barrier method OR maintenance of abstinence must include the time from the beginning of the screening period until 90 days following the last dose of the study treatment.

You may not qualify if:

Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
Active malignancy requiring treatment within the last five years.
Major physical trauma in the last 5 days, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries.
Active tuberculosis or cystic fibrosis.
Severe chronic respiratory disease including chronic obstructive pulmonary disease or pulmonary fibrosis requiring home oxygen \> 5L/min.
Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
Pre-existing pulmonary hypertension.
Severe pre-existing hepatic impairment (presence of cirrhosis, liver function tests (LFTs) ≥ 6x baseline, INR ≥ 2.0).
Pre-existing Chronic Kidney Disease (CKD) stage IIIb or End Stage Renal Disease (ESRD) prior to onset of COVID-19 (stage I, II, and IIIa are acceptable)
Irreversible coagulopathy (e.g., frequently occluded vascular access despite anticoagulation, precipitous platelet drops concurrent with end-organ damage suggesting consumptive process) or irreversible bleeding disorder (e.g., frequent bleeding from vascular access, endotracheal tubes, and foley).
Pneumonia clearly attributable to a non-COVID-19 related process, including aspiration pneumonia or pneumonia that is exclusively bacterial, or originating from a diagnosed alternative virus (e.g., influenza).
Patients who are not full code.
Endotracheal intubation duration ≤ 24 hours.
Moribund-expected survival \< 24 hours.
Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH \< 7.3)

Contact the study team to confirm eligibility.