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

Acute Respiratory Distress Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05354141
• Other study ID #: DB-EF-PHASEIII-0001
• Status: Recruiting
• Phase: Phase 3
• Start date: July 1, 2022
• Est. completion date: August 31, 2025

Study information

• Verified date: February 2024
• Source: Direct Biologics, LLC
• Contact: Bill Arana
• Phone: 1-800-791-1021
• Email: clinicalaffairs[@]directbiologics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 970
• Est. completion date: August 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• ARDS
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Biological:
• ExoFlo
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

Other:
• Intravenous normal saline
Placebo

Locations

Country	Name	City	State
United States	Direct Biologics Investigational Site	Ann Arbor	Michigan
United States	Direct Biologics Investigational Site	Boise	Idaho
United States	Direct Biologics Investigational Site	Boston	Massachusetts
United States	Direct Biologics Investigational Site	Bronx	New York
United States	Direct Biologics Investigational Site	Burlington	Massachusetts
United States	Direct Biologics Investigational Site	Chandler	Arizona
United States	Direct Biologics Investigational Site	Charleston	South Carolina
United States	Direct Biologics Investigational Site	Cincinnati	Ohio
United States	Direct Biologics Investigational Site	Cleveland	Ohio
United States	Direct Biologics Investigational Site	Dallas	Texas
United States	Direct Biologics Investigational Site	Durham	North Carolina
United States	Direct Biologics Investigational Site	Fort Worth	Texas
United States	Direct Biologics Investigational Site	Fullerton	California
United States	Direct Biologics Investigational Site	Houston	Texas
United States	Direct Biologics Investigational Site	Iowa City	Iowa
United States	Direct Biologics Investigational Site	Jackson	Mississippi
United States	Direct Biologics Investigational Site	Little Rock	Arkansas
United States	Direct Biologics Investigational Site	Mesquite	Texas
United States	Direct Biologics Investigational Site	Mount Holly	New Jersey
United States	Direct Biologics Investigational Site	Murray	Utah
United States	Direct Biologics Investigational Site	Orange	California
United States	Direct Biologics Investigational Site	Portland	Oregon
United States	Direct Biologics Investigational Site	Queens	New York
United States	Direct Biologics Investigational Site	Sacramento	California
United States	Direct Biologics Investigational Site	San Francisco	California
United States	Direct Biologics Investigational Site	Sayre	Pennsylvania
United States	Direct Biologics Investigational Site	Silver Spring	Maryland
United States	Direct Biologics Investigational Site	Springfield	Massachusetts
United States	Direct Biologics Investigational Site	Washington	District of Columbia
United States	Direct Biologics Investigational Site	Wichita	Kansas
United States	Direct Biologics Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Direct Biologics, LLC

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   Direct Biologics, LLC