Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)

Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles for Hospitalized Patients With Moderate-to-Severe ARDS: A Phase III Clinical Trial

To evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EVs), ExoFlo, versus placebo for the treatment of hospitalized patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome; ARDS
• Intervention / Treatment: Other: Intravenous normal saline; Biological: ExoFlo

Detailed Description

This is a Phase III, multicenter, randomized, double-blinded, placebo-controlled trial for the treatment of moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

• Study Type: Interventional
• Enrollment (Estimated): 970
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bill Arana; Phone Number: 1-800-791-1021; Email: clinicalaffairs@directbiologics.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Recruiting
      • Direct Biologics Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • Direct Biologics Investigational Site
  • California
    • Davis, California, United States, 95817
      • Recruiting
      • Direct Biologics Investigational Site
    • Irvine, California, United States, 92627
      • Recruiting
      • Direct Biologics Investigational Site
    • Sacramento, California, United States, 95817
      • Recruiting
      • Direct Biologics Investigational Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Direct Biologics Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Direct Biologics Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83712
      • Recruiting
      • Direct Biologics Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Direct Biologics Investigational Site
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Recruiting
      • Direct Biologics Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Direct Biologics Investigational Site
    • Burlington, Massachusetts, United States, 01805
      • Recruiting
      • Direct Biologics Investigational Site
    • Springfield, Massachusetts, United States, 01199
      • Recruiting
      • Direct Biologics Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Direct Biologics Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Direct Biologics Investigational Site
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Recruiting
      • Direct Biologics Investigational Site
  • New York
    • Flushing, New York, United States, 11368
      • Recruiting
      • Direct Biologics Investigational Site
    • Queens, New York, United States, 11040
      • Recruiting
      • Direct Biologics Investigational Site
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Direct Biologics Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Direct Biologics Investigational Site
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Direct Biologics Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • Direct Biologics Investigational Site
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Direct Biologics Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Direct Biologics Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Direct Biologics Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37996
      • Recruiting
      • Direct Biologics Investigational Site
    • Nashville, Tennessee, United States, 37235
      • Recruiting
      • Direct Biologics Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Direct Biologics Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Direct Biologics Investigational Site
    • Houston, Texas, United States, 77030
      • Recruiting
      • Direct Biologics Investigational Site
  • Utah
    • Murray, Utah, United States, 84107
      • Not yet recruiting
      • Direct Biologics Investigational Site
    • Salt Lake City, Utah, United States, 84101
      • Recruiting
      • Direct Biologics Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women aged 18-75 years of age

2. Presence of the following criteria for moderate to severe ARDS as defined by the Berlin Criteria within 24 hours of the first infustion:

   1. Onset within 7 days of known clinical insult or requiring increasing respiratory rate, increasing oxygen flows, or increased work of breathing, and
   2. Bilateral lung opacities not fully explained by pleural effusions, atelectasis, or nodules, and
   3. PaO2/FiO2 (P/F ratio) ≤ 200 mm Hg, and
   4. Invasive or noninvasive ventilation with a minimum PEEP 5 cm H2O or minimum of continuous positive airway pressure (CPAP) 5 cm H2O, or High Flow Nasal Oxygen at ≥ 30 L/min, and
   5. Respiratory failure not fully explained by cardiac failure or fluid overload.

Exclusion Criteria:

1. Lack of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
2. Stated unwillingness to comply with all study procedures and availability for the duration of the study
3. Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
4. Active malignancy requiring treatment within the last two years, with the exception of non-melanoma skin cancers.
5. 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.
6. Duration of mechanical ventilation exceeds 3 days or 72 hours from diagnosis of ARDS.
7. ALT or AST > 8 x Upper Limit of Normal (ULN).
8. Documented history of cirrhosis.
9. DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation.
10. Moribund-expected survival < 24 hours.
11. Severe metabolic disturbances at randomization (e.g., ketoacidosis, pH < 7.2)
12. Patient currently connected to Extracorporeal Membrane Oxygenation at initiation of screening.
13. If the candidate, either a male or female of reproductive potential, is unwilling to two methods 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 method OR maintenance of abstinence must include the time from the beginning of the screening period until Day 61, day of withdrawal or early termination
14. Use of investigational COVID-19 agents or any other investigational agents within 30 days prior to the first dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Normal saline 100 mL	Other: Intravenous normal saline; Placebo
Experimental: Experimental Dose; Normal saline 85 mL and ExoFlo 15 mL	Biological: ExoFlo; Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of 60-day All-cause Mortality	To evaluate the 60-day mortality rate for IMP 15mL as a treatment for moderate-to-severe ARDS compared to placebo. Reducing the mortality rate for hospitalized patients with moderate-to-severe ARDS is a measure of the treatment effect.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to death	Reducing the mortality rate for hospitalized patients moderate-to-severe ARDS is a measure of the treatment effect.	60 days
Ventilator-free days (VFDs)	Number of days for which patients are not on mechanical ventilation.	Day 29
ICU free days	Number of days for which patients are not in the ICU.	Day 29
Oxygen free days	Number of days for which patients are not on oxygen support.	Day 29
Incidence of Treatment Emergent Serious Adverse Events (TESAEs)	Safety comparison performed between IMP 15 mL and placebo arms	61 days

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Direct Biologics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ARDS; Exosome; Extracellular Vesicles; ExoFlo
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome
• Other Study ID Numbers: DB-EF-PHASEIII-0001

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