Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome

Recruiting at 76 trial locations

Overseen By Bill Arana

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Direct Biologics, LLC

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Active malignancy, Major trauma, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

970 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ExoFlo, derived from stem cells, to determine if it helps people with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) breathe easier. The researchers aim to compare ExoFlo's safety and effectiveness against a placebo (a substance with no active treatment) in hospitalized individuals. Those who have developed breathing problems within the past week and are on breathing support might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that ExoFlo is likely to be safe for humans?

Research has shown that ExoFlo, which contains tiny particles from stem cells, is safe to use. One study demonstrated that a 15 mL dose was safe for patients with severe COVID-19-related breathing problems. Another study found that two doses of ExoFlo safely reduced death rates in adults aged 18 to 65 with severe COVID-19 breathing issues. Even with repeated doses, another study reported no negative effects. These findings suggest that ExoFlo is well-tolerated for treating serious lung problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ARDS?

ExoFlo is unique because it utilizes extracellular vesicles, tiny particles that can deliver therapeutic molecules directly to cells, potentially reducing inflammation and repairing lung tissue in Acute Respiratory Distress Syndrome (ARDS). Unlike standard treatments like mechanical ventilation or corticosteroids, which primarily offer supportive care, ExoFlo targets cellular communication and repair at a molecular level. Researchers are excited about ExoFlo because it represents a novel approach that might improve outcomes by addressing the underlying cellular dysfunction in ARDS. This innovative mechanism could lead to more effective and faster recovery for patients.

What evidence suggests that ExoFlo might be an effective treatment for ARDS?

Research has shown that ExoFlo, a treatment derived from bone marrow stem cells, may help treat Acute Respiratory Distress Syndrome (ARDS). In earlier studies, ExoFlo proved safe for patients with severe breathing problems due to COVID-19. Another study on ARDS found that ExoFlo could help reduce symptoms in patients with moderate to severe cases. This treatment uses tiny particles called extracellular vesicles to repair damaged lung tissue and reduce swelling. In this trial, participants will receive either an experimental dose of ExoFlo or a placebo. These early results suggest that ExoFlo could effectively treat ARDS. ^{1 3 4 6 7}

Who Is on the Research Team?

Bill Arana

Principal Investigator

Direct Biologics, LLC

Are You a Good Fit for This Trial?

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 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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ExoFlo

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.

How Is the Trial Designed?

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

ExoFlo is already approved in United States for the following indications:

Approved in United States as ExoFlo for:

• Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19

Who Is Running the Clinical Trial?

Direct Biologics, LLC

Lead Sponsor

Trials

11

Recruited

1,100+

Published Research Related to This Trial

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]

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]

In a study of 24 patients with severe COVID-19, treatment with ExoFlo™, derived from bone marrow stem cells, showed a high safety profile with no adverse events reported within 72 hours and an 83% survival rate.

Patients treated with ExoFlo experienced significant improvements in clinical status, including a 192% increase in oxygenation levels and notable reductions in inflammatory markers, suggesting its potential as a therapeutic option for severe COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19. Sengupta, V., Sengupta, S., Lazo, A., et al.[2021]

Mesenchymal stem cell-derived exosomes (MSC-exosomes) have shown promise in effectively reducing inflammation and aiding cell repair in conditions like acute lung injury and acute respiratory distress syndrome (ALI/ARDS).

The research landscape indicates that the USA and China are leading in MSC-exosome studies, with a notable focus on their potential in treating COVID-19-related ALI/ARDS, highlighting the growing importance of this area in current medical research.

NCBI (Pubmed)

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. Zhou, W., Hu, S., Wu, Y., et al.[2023]

The phase 2a trial involving 60 patients with moderate to severe ARDS found that a single intravenous dose of bone-marrow-derived mesenchymal stromal cells (MSCs) was safe, with no serious MSC-related adverse events reported.

While the 28-day mortality rate was higher in the MSC group (30%) compared to placebo (15%), this difference was not statistically significant, indicating that further research is needed to evaluate the efficacy of MSC treatment in ARDS.

NCBI (Pubmed)

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. Matthay, MA., Calfee, CS., Zhuo, H., et al.[2022]

Mesenchymal stromal cell-derived therapies (MDTs) significantly reduce lung injury scores and improve survival rates in animal models of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), based on a meta-analysis of 17 studies.

MDTs work by decreasing inflammation in the lungs, as evidenced by reduced neutrophil infiltration and changes in inflammatory mediator levels, suggesting a potential mechanism for their therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of mesenchymal stromal cell-derived therapies for acute respiratory distress syndrome-a meta-analysis of preclinical trials. Wang, F., Fang, B., Qiang, X., et al.[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]

Stem cell-derived exosomes show promise as a therapeutic strategy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) by modulating inflammation and promoting tissue repair.

These exosomes can deliver bioactive components to recipient cells, aiding in the reconstruction of lung tissue and preventing pulmonary fibrosis, highlighting their potential for a cell-free treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cell derived exosomes-based therapy for acute lung injury and acute respiratory distress syndrome: A novel therapeutic strategy. Xu, B., Chen, SS., Liu, MZ., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37356708/

A Randomized, Placebo-Controlled Dosing Clinical Trial The 15 mL dose of ExoFlo was found to be safe in patients with severe or critical COVID-19-associated respiratory failure.

2. journal.chestnet.org journal.chestnet.org/article/S0012-3692(23)00926-1/fulltext

Bone Marrow Mesenchymal Stem Cell-Derived Extracellular ... This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05354141

NCT05354141 | Extracellular Vesicle Treatment for Acute ... This is a Phase III, multicenter, randomized, double-blinded, placebo-controlled trial for the treatment of moderate-to-severe Acute Respiratory Distress ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05787288

NCT05787288 | A Clinical Study on Safety and ... This clinical study aims to investigate the safety and efficacy of nebulized inhalation of extracellular vesicles derived from mesenchymal stem cells ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2213007124001102

A novel extracellular vesicle paradigm for the treatment of ... This case illustrates the potential for a BM-MSC EV product to manage COVID ARDS and highlights this BM-MSC EV IP as a novel, convenient and potentially ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11295994/

A novel extracellular vesicle paradigm for the treatment of ... No adverse events occurred despite repeated dosing of investigational product, highlighting safety of this potential therapy for ARDS. Keywords: ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0012369223009261

Bone Marrow Mesenchymal Stem Cell-Derived ... Two doses of ExoFlo safely and significantly reduced mortality in patients aged 18 to 65 years with respiratory failure caused by critical or severe COVID-19.