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

Phase 3

Recruiting

• Conditions: Acute Respiratory Distress Syndrome; ARDS
• Interventions: Other: Intravenous normal saline; Biological: ExoFlo

• Registration Number: NCT05354141
• Lead Sponsor: Direct Biologics, LLC

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).

Study Timeline

• Study First Submitted: 2022-04-27
• Study First Submitted QC: 2022-04-27
• Study First Posted: 2022-04-29
• Study Start: 2022-07-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-21
• Last Update Posted: 2024-11-25
• Primary Completion: 2025-03-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 970

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Intravenous normal saline	Normal saline 100 mL
Experimental Dose	ExoFlo	Normal saline 85 mL and ExoFlo 15 mL

Primary Outcome Measures

Name	Time	Method
Evaluation of 60-day All-cause Mortality	60 days	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Direct Biologics Investigational Site; 🇺🇸 Salt Lake City, Utah, United States