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

Purpose

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).

Conditions

  • Acute Respiratory Distress Syndrome
  • ARDS

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Multicenter, randomized, double-blinded, placebo-controlled trial
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Double-Blinded

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Direct Biologics Investigational Site
Chandler, Arizona 85224

Direct Biologics Investigational Site
Little Rock, Arkansas 72205

Direct Biologics Investigational Site
Fullerton, California 92835

Direct Biologics Investigational Site
Orange, California 92868

Direct Biologics Investigational Site
Sacramento, California 95817

Direct Biologics Investigational Site
San Francisco, California 94143

Direct Biologics Investigational Site
Washington, District of Columbia 20010

Direct Biologics Investigational Site
Boise, Idaho 83712

Direct Biologics Investigational Site
Iowa City, Iowa 52242

Direct Biologics Investigational Site
Wichita, Kansas 67214

Direct Biologics Investigational Site
Silver Spring, Maryland 20910

Direct Biologics Investigational Site
Boston, Massachusetts 02115

Direct Biologics Investigational Site
Burlington, Massachusetts 01805

Direct Biologics Investigational Site
Springfield, Massachusetts 01199

Direct Biologics Investigational Site
Ann Arbor, Michigan 48109

Direct Biologics Investigational Site
Jackson, Mississippi 39202

Direct Biologics Investigational Site
Mount Holly, New Jersey 08060

Direct Biologics Investigational Site
Bronx, New York 10467

Direct Biologics Investigational Site
Queens, New York 11040

Direct Biologics Investigational Site
Durham, North Carolina 27710

Direct Biologics Investigational Site
Winston-Salem, North Carolina 27157

Direct Biologics Investigational Site
Cincinnati, Ohio 45219

Direct Biologics Investigational Site
Cleveland, Ohio 44106

Direct Biologics Investigational Site
Portland, Oregon 97239

Direct Biologics Investigational Site
Sayre, Pennsylvania 18840

Direct Biologics Investigational Site
Charleston, South Carolina 29425

Direct Biologics Investigational Site
Dallas, Texas 75246

Direct Biologics Investigational Site
Fort Worth, Texas 76104

Direct Biologics Investigational Site
Houston, Texas 77030

Direct Biologics Investigational Site
Murray, Utah 84107

More Details

NCT ID
NCT05354141
Status
Recruiting
Sponsor
Direct Biologics, LLC

Study Contact

Bill Arana
1-800-791-1021
clinicalaffairs@directbiologics.com

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).