Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for ARDS (EXIT-ARDS)

Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for Acute Respiratory Distress Syndrome: A Phase I/II Clinical Trial

To evaluate the safety and efficacy of intravenous(IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles(EV), ExoFlo, as treatment for Acute Respiratory Distress Syndrome.

Study Overview

• Status: Withdrawn
• Conditions: ARDS, Human
• Intervention / Treatment: Other: Saline; Drug: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles

Detailed Description

To evaluate the safety and efficacy of intravenous(IV) administration of bone marrow mesenchymal stem cell-derived extracellular vesicles (EV), ExoFlo, as treatment for Acute Respiratory Distress Syndrome. ExoFlo is also referred to as Investigational Product (IP) throughout the protocol. The duration of the study is 60 days, and the endpoints are as follows:

Primary Endpoint:

1. The incidence of serious adverse events.
2. All-Cause Mortality at 28 days.

Secondary Endpoints:

1. Ventilator-free days at 28days.
2. Improvement in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio from pre-infusion baseline(Day 0)to Day 7.

The study population will consist of 81 inpatient adult patients between 18 and 85 years of age with moderate to severe ARDS as defined by modified Berlin's criteria. Patients will be randomized via Interactive Response Technology to one of the following 3 treatment arms:

1. PLACEBO: Normal saline 100 mL
2. EXPERIMENTAL: IP 10 mL mixed with Normal Saline 90 mL
3. EXPERIMENTAL: IP 15 mL mixed with Normal Saline 85 mL

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female aged 18-85.
4. Moderate to severe ARDS as defined by modified Berlin definition (See Section 2.2.1), 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.
5. 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.
6. 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.

Exclusion Criteria:

1. Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
2. Active malignancy requiring treatment within the last five years.
3. Major physical trauma in the last 2 days, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries, such that not one or more injury may be undiagnosed at time of screening.
4. Diagnosis or suspected diagnosis of sepsis without basic microbiology cultures (urinalysis, urine culture, two sets of blood cultures, respiratory culture, at least a standard respiratory viral panel PCR) being collected prior to screening. (Note: Standard respiratory viral panel is defined by at least PCR testing for Adenovirus, Influenza A, Influenza B, Parainfluenza 1-3, Rhinovirus/Enterovirus, and RSV.)
5. Duration of mechanical ventilation exceeds 5 days or 120 hours.
6. Severe pre-existing organ dysfunction prior to admission, as evidenced by being currently listed on one or more organ transplant list, or intermittent Hemodialysis (HD) or Peritoneal Dialysis.
7. Presence of severe hematologic disorder or coagulopathy, such as Disseminated Intravascular Coagulopathy, as evidenced by the activation of a Massive Transfusion Protocols (as defined by the rapid administration of packed Red Blood Cells, Fresh Frozen Plasma and Platelets in fixed ratios, including at least 6 packed Red Blood Cells, within a 24 hour period) within 72 hours or frequent thrombosis of catheters (as specified by replacing 2 catheters or more within a 72 hour period of new placement) within 72 hours.
8. Severe anemia or myelodysplastic syndrome requiring more than 10 units of packed Red Blood Cells transfused within the last 12 months.
9. Patient is currently connected to Extracorporal Membrane Oxygenation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Saline; Saline	Other: Saline; Placebo Saline
Experimental: 10mL Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles; ExoFlo (Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles)	Drug: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles; Injectable; Other Names: ExoFlo
Experimental: 15mL Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles; ExoFlo (Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles)	Drug: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles; Injectable; Other Names: ExoFlo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of serious adverse events.	60 days
Number to patients with All-Cause Mortality at 28 days	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Ventilator-free days at 28days	28 days
Change 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 SpO2daily.	7 days

Collaborators and Investigators

• Sponsor: Direct Biologics, LLC
• Investigators: Study Director: Bill Arana, Direct Biologics, LLC

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: July 26, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: ARDS; ExoFlo; EXIT-ARDS; Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles; Direct Biologics
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Respiratory Distress Syndrome
• Other Study ID Numbers: DB-EF-EXITARDS-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No