Covid19NCT04657458
Expanded Access for Use of bmMSC-Derived Extracellular Vesicles in Patients With COVID-19 Associated ARDS
A study testing ExoFlo in people with Covid19 and ARDS, run by Direct Biologics, LLC.
Trial summary
ExoFlo, Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Allograft Product, Infusion Treatment is currently being studied in Protocol DB-EF-PhaseIII-0001 in patients COVID-19 associated moderate to severe acute respiratory distress syndrome (ARDS). Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- ExoFlo
- Type of treatment
- Injection or infusion
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- Phase
- Expanded access
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- Adult, Older adult
Who may be able to join
- Provision of informed consent by self or proxy.
- Stated willingness to comply with study protocol.
- Male or female of any age ≥ 18 years of age
- May be pregnant unless the patient has one or more conditions listed under Exclusion Criteria #3.
- Positive Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) SARS-CoV-2.
- Moderate to severe ARDS as defined by timing within ten days of known clinical insult or new or worsening respiratory symptoms, bilateral opacities not fully explained by effusions or lung collapse, and respiratory failure not fully explained by cardiac failure or fluid overload, minimum 5 cm H2O PEEP on mechanical ventilation, and PaO2/FiO2 ≤ 200 mmHg (if using an estimated P/F ratio, a S/F ≤ 235 is accepted).
- Acute presentation of hypoxic respiratory failure requiring noninvasive oxygen support OR mechanical ventilation (MV).
Who cannot join
- Active malignancy requiring treatment within the last two years, with the exception of non-melanoma skin cancers.
- Patients who are not full code.
- Pregnant patients with current or past history of eclampsia, preeclampsia, hemolysis, elevated liver enzymes, or low platelet count (HELLP) syndrome during pregnancy.
- New York Heart Association (NYHA) Functional Class III (symptoms present during ordinary activities) or IV Heart Failure (symptoms present at rest) or listed for heart transplant.
- Chronic Kidney Disease (CKD) Stage IV (GFR 15-29 mL/min/1.73m2) and Stage V (GFR < 15 mL/min/1.73m2) or listed for kidney transplant.
- Hepatic Impairment with Model for End-Stage Liver Disease (MELD) score ≥ 30 or listed for liver transplant.
About this study
Official title: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment: Expanded Access Protocol for Patients With COVID-19 Associated ARDS
ExoFlo, Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Allograft Product, Infusion Treatment is currently being studied in Protocol DB-EF-PhaseIII-0001 in patients COVID-19 associated moderate to severe acute respiratory distress syndrome (ARDS). This expanded access protocol is an open label study intended to provide ExoFlo to critically ill patients who do not qualify for the Phase III randomized controlled trial (RCT) because they
- Do not meet phase III eligibility criteria at current phase III sites.
- Do meet phase III eligibility criteria but cannot access phase III sites.
- Do not meet phase III eligibility criteria \& cannot access phase III sites.
Read the detailed description
Objectives:
First, to provide Investigational Medicinal Product (IMP) to patients with COVID-19 associated moderate to severe ARDS who do not qualify for Protocol DB-EF-PHASEIII-0001. Secondarily, to collect safety and efficacy data.
Endpoints:
Primary Endpoint:
- 60-day All-Cause Mortality
Secondary Endpoints:
- Incidence of serious adverse events (SAEs).
- Ventilator-free days (VFDs).
- Time to discharge.
Exploratory Endpoints:
- Acute phase reactants: C-reactive protein (CRP), D-dimer, and Ferritin change from Baseline on Days 3, 5, 7, 10, 15, and 29 for subjects who are still hospitalized.
- Sequential Organ Failure Assessment (SOFA) Score change from Baseline on Days 15, and 29 for subjects who are still hospitalized.
- Improvement in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio from pre-infusion baseline (Day 0) to Day 7. PaO2 may be calculated from arterial blood gas (ABG) or imputed from the SpO2 daily.
Number of subjects: ≤200
Phase: Phase II /Expanded Access Protocol for Intermediate Population
- Conditions
- Covid19, ARDS, Hypoxia, Cytokine Storm
- Being tested
- ExoFlo
- Keywords
- COVID-19, ARDS, SARS-CoV-2
- Medical subject headings
- COVID-19, Hypoxia, Cytokine Release Syndrome
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies 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
- Expanded access
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
- NCT04657458
- Sponsor's protocol ID
- DB-EF-EXPANDEDACCESS-001
- Status last verified
- Nov 2024
- First submitted
- 7 Dec 2020
- Last updated
- 22 Nov 2024
- Results posted
- No
Publications
Sengupta V, Qian S, Ransom JT, Suzuki S, Park DJ, Melson TI, Williams BP, Walsh JJ, Awili M, Mann JM, Moseley TA. Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle Treatment of Respiratory Failure from COVID-19: Endpoint Analysis of Expanded Access Safety Trial. Stem Cell Rev Rep. 2026 Jul;22(5):2612-2621. doi: 10.1007/s12015-026-11137-1. Epub 2026 May 11.
PubMed 42113080
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 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: Expanded Access Protocol for Patients With COVID-19 Associated ARDS
- ClinicalTrials.gov ID
- NCT04657458
- Acronym / sponsor ID
- DB-EF-EXPANDEDACCESS-001
- Conditions
- Covid19, ARDS, Hypoxia, Cytokine Storm
- Keywords
- COVID-19, ARDS, SARS-CoV-2
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- Lead sponsor
- Direct Biologics, LLCIndustry (pharma, biotech, devices)
- First posted
- 8 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
ExoFlo, Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Allograft Product, Infusion Treatment is currently being studied in Protocol DB-EF-PhaseIII-0001 in patients COVID-19 associated moderate to severe acute respiratory distress syndrome (ARDS). This expanded access protocol is an open label study intended to provide ExoFlo to critically ill patients who do not qualify for the Phase III randomized controlled trial (RCT) because they
- Do not meet phase III eligibility criteria at current phase III sites.
- Do meet phase III eligibility criteria but cannot access phase III sites.
- Do not meet phase III eligibility criteria \& cannot access phase III sites.
Detailed description
Objectives:
First, to provide Investigational Medicinal Product (IMP) to patients with COVID-19 associated moderate to severe ARDS who do not qualify for Protocol DB-EF-PHASEIII-0001. Secondarily, to collect safety and efficacy data.
Endpoints:
Primary Endpoint:
- 60-day All-Cause Mortality
Secondary Endpoints:
- Incidence of serious adverse events (SAEs).
- Ventilator-free days (VFDs).
- Time to discharge.
Exploratory Endpoints:
- Acute phase reactants: C-reactive protein (CRP), D-dimer, and Ferritin change from Baseline on Days 3, 5, 7, 10, 15, and 29 for subjects who are still hospitalized.
- Sequential Organ Failure Assessment (SOFA) Score change from Baseline on Days 15, and 29 for subjects who are still hospitalized.
- Improvement in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio from pre-infusion baseline (Day 0) to Day 7. PaO2 may be calculated from arterial blood gas (ABG) or imputed from the SpO2 daily.
Number of subjects: ≤200
Phase: Phase II /Expanded Access Protocol for Intermediate Population
Study design
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Provision of informed consent by self or proxy.
- Stated willingness to comply with study protocol.
- Male or female of any age ≥ 18 years of age
- May be pregnant unless the patient has one or more conditions listed under Exclusion Criteria #3.
- Positive Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) SARS-CoV-2.
Key exclusion criteria (6 listed)
- Active malignancy requiring treatment within the last two years, with the exception of non-melanoma skin cancers.
- Patients who are not full code.
- Pregnant patients with current or past history of eclampsia, preeclampsia, hemolysis, elevated liver enzymes, or low platelet count (HELLP) syndrome during pregnancy.
- New York Heart Association (NYHA) Functional Class III (symptoms present during ordinary activities) or IV Heart Failure (symptoms present at rest) or listed for heart transplant.
- Chronic Kidney Disease (CKD) Stage IV (GFR 15-29 mL/min/1.73m2) and Stage V (GFR < 15 mL/min/1.73m2) or listed for kidney transplant.
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 | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Derived from this study: PubMed 42113080Sengupta V, Qian S, Ransom JT, Suzuki S, Park DJ, Melson TI, Williams BP, Walsh JJ, Awili M, Mann JM, Moseley TA. Bone Marrow Mesenchymal Stem Cell Extracellular Vesicle Treatment of Respiratory Failure from COVID-19: Endpoint Analysis of Expanded Access Safety Trial. Stem Cell Rev Rep. 2026 Jul;22(5):2612-2621. doi: 10.1007/s12015-026-11137-1. Epub 2026 May 11.
- Direct Biologics, LLCLink provided by the sponsor.
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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
Questions about this trial
What is this clinical trial studying?
A study testing ExoFlo in people with Covid19 and ARDS, run by Direct Biologics, LLC.
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 7 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04657458, 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 22 Nov 2024.