COVID-19Phase 2EXIT-COVID19NCT04493242
Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS
A Phase 2 study testing ExoFlo and Intravenous normal saline in people with COVID-19 and ARDS, run by Direct Biologics, LLC at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- What is being tested?
- ExoFlo and Intravenous normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 6 sitesUnited States
- Study dates
- 24 Sep 2020to 22 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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)
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Direct Biologics Investigational Site
Anaheim, California, 92805
Direct Biologics Investigational Site
Houston, Texas, 77024
Direct Biologics Investigational Site
Lubbock, Texas, 79410
Direct Biologics Investigational Site
Mesquite, Texas, 75149
Direct Biologics Investigational Site
Sayre, Pennsylvania, 18840
Direct Biologics Investigational Site
Sheffield, Alabama, 35660
About this study
Official title: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS): A Phase II Clinical Trial
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.
Read the detailed description
This is a Phase II, double-blinded, placebo-controlled, randomized controlled trial that enrolled 102 subjects that were admitted with COVID-19 associated moderate-to-severe ARDS across 6 sites in the United States.
- Being tested
- ExoFlo, Intravenous normal saline
- Keywords
- COVID-19, ARDS, Extracellular Vesicles, Exosome
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExoFloBiological
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles
Intravenous normal salineOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Normal saline 100 mL Receives: Other: Intravenous normal saline |
| Experimental Dose 1 | Experimental | Normal saline 90 mL and ExoFlo 10 mL Receives: Biological: ExoFlo |
| Experimental Dose 2 | Experimental | Normal saline 85 mL and ExoFlo 15 mL Receives: Biological: ExoFlo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 60 days
Secondary outcomes (5)
Overall Survival Rates
Reducing the mortality rate for hospitalized patients with COVID-19 associated ARDS is a measure of the treatment effect.
Measured: Days 15, 30, 60
Proportion of Discharged Patients
Discharge is an unbiased measure of overall clinical improvement.
Measured: Days 7, 30, 60
Time to Discharge
Discharge is an unbiased measure of overall clinical improvement.
Measured: Number of days from the date of randomization until documented discharge from hospital, up to 60 days.
Incidence of Treatment Emergent Serious Adverse Events
Safety comparison performed between IP 15 mL and placebo arms
Measured: 61 days
Ventilation Free Days
Number of days for which patients are not on mechanical ventilation.
Measured: Within 60 days of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2020
- Study start24 Sep 2020
- Primary completion1 May 2021
- Study completion22 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Direct Biologics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bill Arana, Study director, Direct Biologics, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04493242
- Sponsor's protocol ID
- DB-EF-PHASEII-001
- Acronym
- EXIT-COVID19
- Status last verified
- Feb 2024
- First submitted
- 29 Jul 2020
- Last updated
- 13 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Publications
Lightner AL, Sengupta V, Qian S, Ransom JT, Suzuki S, Park DJ, Melson TI, Williams BP, Walsh JJ, Awili M. Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial. Chest. 2023 Dec;164(6):1444-1453. doi: 10.1016/j.chest.2023.06.024. Epub 2023 Jun 23.
PubMed 37356708
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS): A Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT04493242
- Acronym / sponsor ID
- EXIT-COVID19 / DB-EF-PHASEII-001
- Keywords
- COVID-19, ARDS, Extracellular Vesicles, Exosome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Direct Biologics, LLCIndustry (pharma, biotech, devices)
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 1 May 2021 (actual)
- Study completion
- 22 May 2021 (actual)
- First posted
- 30 Jul 2020 (actual)
- Results
- Posted 11 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase II, double-blinded, placebo-controlled, randomized controlled trial that enrolled 102 subjects that were admitted with COVID-19 associated moderate-to-severe ARDS across 6 sites in the United States.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Intravenous normal salineNormal saline 100 mL |
| Experimental Dose 1 | Experimental | Biological: ExoFloNormal saline 90 mL and ExoFlo 10 mL |
| Experimental Dose 2 | Experimental | Biological: ExoFloNormal saline 85 mL and ExoFlo 15 mL |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExoFloIntravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles | Biological | Experimental Dose 1, Experimental Dose 2 |
| Intravenous normal salinePlacebo | Other | Placebo |
Primary outcome
Evaluation of 60-day Mortality Rate
Time frame: 60 days
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.
5 secondary outcomes
Overall Survival Rates
Time frame: Days 15, 30, 60
Proportion of Discharged Patients
Time frame: Days 7, 30, 60
Time to Discharge
Time frame: Number of days from the date of randomization until documented discharge from hospital, up to 60 days.
Incidence of Treatment Emergent Serious Adverse Events
Time frame: 61 days
Ventilation Free Days
Time frame: Within 60 days of follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37356708Lightner AL, Sengupta V, Qian S, Ransom JT, Suzuki S, Park DJ, Melson TI, Williams BP, Walsh JJ, Awili M. Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial. Chest. 2023 Dec;164(6):1444-1453. doi: 10.1016/j.chest.2023.06.024. Epub 2023 Jun 23.
- Direct Biologics, LLCLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bill Arana study director
Direct Biologics, LLC
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ExoFlo and Intravenous normal saline in people with COVID-19 and ARDS, run by Direct Biologics, LLC at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of 60-day Mortality Rate (time frame: 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04493242, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.