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 Sex
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
Birmingham 4049979, Alabama 4829764 35233

Direct Biologics Investigational Site
Chandler 5289282, Arizona 5551752 85224

Direct Biologics Investigational Site
Phoenix 5308655, Arizona 5551752 85012

Direct Biologics Investigational Site
Little Rock 4119403, Arkansas 4099753 72205

Direct Biologics Investigational Site
Davis 5341704, California 5332921 95817

Direct Biologics Investigational Site
Fullerton 5351247, California 5332921 92835

Direct Biologics Investigational Site
Irvine 5359777, California 5332921 92627

Direct Biologics Investigational Site
Orange 5379513, California 5332921 92868

Direct Biologics Investigational Site
Sacramento 5389489, California 5332921 95817

Direct Biologics Investigational Site
San Francisco 5391959, California 5332921 94143

Direct Biologics Investigational Site
Washington D.C. 4140963, District of Columbia 4138106 20010

Direct Biologics Investigational Site
Jacksonville 4160021, Florida 4155751 32224

Direct Biologics Investigational Site
Boise 5586437, Idaho 5596512 83712

Direct Biologics Investigational Site
Iowa City 4862034, Iowa 4862182 52242

Direct Biologics Investigational Site
Wichita 4281730, Kansas 4273857 67214

Direct Biologics Investigational Site
Silver Spring 4369596, Maryland 4361885 20910

Direct Biologics Investigational Site
Boston 4930956, Massachusetts 6254926 02115

Direct Biologics Investigational Site
Burlington 4931737, Massachusetts 6254926 01805

Direct Biologics Investigational Site
Springfield 4951788, Massachusetts 6254926 01199

Direct Biologics Investigational Site
Ann Arbor 4984247, Michigan 5001836 48109

Direct Biologics Investigational Site
Detroit 4990729, Michigan 5001836 48202

Direct Biologics Investigational Site
Jackson 4431410, Mississippi 4436296 39202

Direct Biologics Investigational Site
Flushing 5117472, New York 5128638 11368

Direct Biologics Investigational Site
Queens 5133273, New York 5128638 11040

Direct Biologics Investigational Site
The Bronx 5110266, New York 5128638 10467

Direct Biologics Investigational Site
Durham 4464368, North Carolina 4482348 27710

Direct Biologics Investigational Site
Winston-Salem 4499612, North Carolina 4482348 27157

Direct Biologics Investigational Site
Cincinnati 4508722, Ohio 5165418 45219

Direct Biologics Investigational Site
Cleveland 5150529, Ohio 5165418 44106

Direct Biologics Investigational Site
Portland 5746545, Oregon 5744337 97239

Direct Biologics Investigational Site
Charleston 4574324, South Carolina 4597040 29425

Direct Biologics Investigational Site
Knoxville 4634946, Tennessee 4662168 37996

Direct Biologics Investigational Site
Nashville 4644585, Tennessee 4662168 37235

Direct Biologics Investigational Site
Dallas 4684888, Texas 4736286 75246

Direct Biologics Investigational Site
Fort Worth 4691930, Texas 4736286 76104

Direct Biologics Investigational Site
Houston 4699066, Texas 4736286 77030

Direct Biologics Investigational Site
Murray 5778755, Utah 5549030 84107

Direct Biologics Investigational Site
Salt Lake City 5780993, Utah 5549030 84101

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).