Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome

Recruiting in Palo Alto (17 mi)

+74 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Direct Biologics, LLC

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Active malignancy, Major trauma, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment where tiny particles from bone marrow cells are used to help patients with severe lung problems by reducing inflammation and repairing lung damage.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used investigational agents within 30 days before the trial starts.

What data supports the effectiveness of the treatment ExoFlo for acute respiratory distress syndrome?

Research shows that ExoFlo, derived from stem cells, has been effective in improving lung function and reducing inflammation in patients with severe COVID-19, which often involves acute respiratory distress syndrome. In a study, patients treated with ExoFlo showed significant improvements in oxygen levels and immune function, suggesting its potential as a treatment for similar lung conditions. ^{1 2 3 4 5}

Is the extracellular vesicle treatment safe for humans?

Research shows that extracellular vesicle treatments, like ExoFlo, have been tested in humans for conditions like severe COVID-19 and have shown a good safety profile with no adverse events observed shortly after treatment. ^{1 2 3 4 6}

How is the ExoFlo treatment different from other treatments for acute respiratory distress syndrome (ARDS)?

ExoFlo is unique because it uses tiny particles from stem cells called extracellular vesicles to help reduce inflammation and repair lung damage, unlike traditional treatments that don't target the underlying causes of ARDS. This approach offers a new way to treat ARDS by harnessing the natural healing properties of stem cells without using the whole cells themselves. ^{1 2 3 7 8}

Research Team

Bill Arana

Principal Investigator

Direct Biologics, LLC

Eligibility Criteria

This trial is for adults aged 18-75 with moderate-to-severe ARDS, as defined by the Berlin Criteria, and who have been on a ventilator for less than 3 days. Excluded are those with certain liver enzyme levels, severe disabilities, pregnant women, recent investigational drug use, active malignancy requiring treatment (except skin cancer), unwillingness to follow study procedures or use effective birth control.

Inclusion Criteria

I am between 18 and 75 years old.

I have been diagnosed with severe lung distress recently.

Exclusion Criteria

I have not experienced major physical trauma or injuries in the last 2 days.

Your ALT or AST levels are more than 8 times the normal limit.

Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous administration of ExoFlo or placebo for the treatment of moderate-to-severe ARDS

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days

Treatment Details

Interventions

• ExoFlo (Extracellular Vesicles)

Trial Overview The EXTINGUISH ARDS trial tests the safety and effectiveness of ExoFlo—an IV therapy using extracellular vesicles from bone marrow stem cells—against a saline placebo in hospitalized patients with moderate-to-severe ARDS to see if it can improve their lung function.

Participant Groups

Group I: Experimental Dose Experimental Treatment 1 Intervention

Normal saline 85 mL and ExoFlo 15 mL

Group II: Placebo Placebo Group 1 Intervention

Normal saline 100 mL

Who Is Running the Clinical Trial?

Direct Biologics, LLC

Lead Sponsor

Trials

11

Recruited

1,100+

Findings from Research

The study involving 102 patients with severe COVID-19 and moderate to severe ARDS found that the 15 mL dose of ExoFlo was safe, with no treatment-related adverse events reported.

In a post hoc analysis, the 15 mL ExoFlo treatment significantly reduced 60-day mortality in younger patients (ages 18 to 65) compared to placebo, suggesting it may be an effective treatment option for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lightner, AL., Sengupta, V., Qian, S., et al.[2023]

Mesenchymal stem cells show great potential for treating acute respiratory distress syndrome (ARDS), primarily through the action of their extracellular vesicles (EVs), which can transfer beneficial substances to help reduce inflammation in the lungs.

Extracellular vesicles have demonstrated similar therapeutic effects as the stem cells themselves, making them a promising candidate for clinical use due to their advantages over whole cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Abraham, A., Krasnodembskaya, A.[2021]

Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) show promise as a treatment for acute respiratory distress syndrome (ARDS) due to their ability to regulate growth factors and cytokines, which can help reduce inflammation and repair cell injury.

MSC-EVs have demonstrated potent therapeutic effects and biocompatibility, making them a potential alternative treatment option for ARDS, although the review also discusses their advantages and limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracellular Vesicles Derived from Mesenchymal Stem Cells: A Potential Biodrug for Acute Respiratory Distress Syndrome Treatment. Sun, H., Zhang, T., Gao, J.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

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. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

A Bibliometric Analysis of Mesenchymal Stem Cell-Derived Exosomes in Acute Lung Injury/Acute Respiratory Distress Syndrome from 2013 to 2022. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Stem cell derived exosomes-based therapy for acute lung injury and acute respiratory distress syndrome: A novel therapeutic strategy. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The efficacy of mesenchymal stromal cell-derived therapies for acute respiratory distress syndrome-a meta-analysis of preclinical trials. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Extracellular Vesicles Derived from Mesenchymal Stem Cells: A Potential Biodrug for Acute Respiratory Distress Syndrome Treatment. [2022]