Clinical trial NCT05354141: Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)
Official title: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles for Hospitalized Patients With Moderate-to-Severe ARDS: A Phase III Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
ARDS
Keywords: ExoFlo
Extracellular Vesicles
Exosome
ARDS
Lead sponsor: Direct Biologics, LLC
Sponsor class: INDUSTRY
First posted: 2022-04-29
Enrollment: 970
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, randomized, double-blinded, placebo-controlled trial
Primary purpose: TREATMENT

Brief 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).

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of 60-day All-cause Mortality
timeFrame: 60 days
Secondary outcomes:
measure: Time to death
timeFrame: 60 days
measure: Ventilator-free days (VFDs)
timeFrame: Day 29
measure: Oxygen free days
timeFrame: Day 29
measure: ICU free days
timeFrame: Day 29
measure: Incidence of Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: 61 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Direct Biologics Investigational Site
state: Alabama
city: Chandler
country: United States
facility: Direct Biologics Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Direct Biologics Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Direct Biologics Investigational Site
state: Arkansas
city: Davis
country: United States
facility: Direct Biologics Investigational Site
state: California
city: Fullerton
country: United States
facility: Direct Biologics Investigational Site
state: California
city: Irvine
country: United States
facility: Direct Biologics Investigational Site
state: California
city: Orange
country: United States
facility: Direct Biologics Investigational Site
state: California
city: Sacramento
country: United States
facility: Direct Biologics Investigational Site
state: California
city: San Francisco
country: United States
facility: Direct Biologics Investigational Site
state: California
city: Washington
country: United States
facility: Direct Biologics Investigational Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Direct Biologics Investigational Site
state: Florida
city: Boise
country: United States
facility: Direct Biologics Investigational Site
state: Idaho
city: Iowa City
country: United States
facility: Direct Biologics Investigational Site
state: Iowa
city: Wichita
country: United States
facility: Direct Biologics Investigational Site
state: Kansas
city: Silver Spring
country: United States
facility: Direct Biologics Investigational Site
state: Maryland
city: Boston
country: United States
facility: Direct Biologics Investigational Site
state: Massachusetts
city: Burlington
country: United States
facility: Direct Biologics Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Direct Biologics Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Direct Biologics Investigational Site
state: Michigan
city: Detroit
country: United States
facility: Direct Biologics Investigational Site
state: Michigan
city: Jackson
country: United States
facility: Direct Biologics Investigational Site
state: Mississippi
city: Bronx
country: United States
facility: Direct Biologics Investigational Site
state: New York
city: Flushing
country: United States
facility: Direct Biologics Investigational Site
state: New York
city: Queens
country: United States
facility: Direct Biologics Investigational Site
state: New York
city: Durham
country: United States
facility: Direct Biologics Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Direct Biologics Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Direct Biologics Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Direct Biologics Investigational Site
state: Ohio
city: Portland
country: United States
facility: Direct Biologics Investigational Site
state: Oregon
city: Charleston
country: United States
facility: Direct Biologics Investigational Site
state: South Carolina
city: Knoxville
country: United States
facility: Direct Biologics Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Direct Biologics Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Direct Biologics Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Direct Biologics Investigational Site
state: Texas
city: Houston
country: United States
facility: Direct Biologics Investigational Site
state: Texas
city: Murray
country: United States
facility: Direct Biologics Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Direct Biologics Investigational Site
state: Utah
Study officials:
affiliation: Direct Biologics, LLC
name: Bill Arana
role: STUDY_DIRECTOR
References: