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

Study Overview
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Brief Summary
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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
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This is a Phase III, multicenter, randomized, double-blinded, placebo-controlled trial for the treatment of moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

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

Conditions
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Acute Respiratory Distress Syndrome, ARDS

Intervention / Treatment
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* Biological: ExoFlo
* Other: Intravenous normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18-75 years of age Presence of the following criteria for moderate to severe ARDS as defined by the Berlin Criteria within 24 hours of the first infustion: Onset within 7 days of known clinical insult or requiring increasing respiratory rate, increasing oxygen flows, or increased work of breathing, and Bilateral lung opacities not fully explained by pleural effusions, atelectasis, or nodules, and PaO2/FiO2 (P/F ratio) ≤ 200 mm Hg, and 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 Respiratory failure not fully explained by cardiac failure or fluid overload. Exclusion Criteria: Lack of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy). Stated unwillingness to comply with all study procedures and availability for the duration of the study Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent. Active malignancy requiring treatment within the last two years, with the exception of non-melanoma skin cancers. 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. Duration of mechanical ventilation exceeds 3 days or 72 hours from diagnosis of ARDS. ALT or AST > 8 x Upper Limit of Normal (ULN). Documented history of cirrhosis. DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation. Moribund-expected survival < 24 hours. Severe metabolic disturbances at randomization (e.g., ketoacidosis, pH < 7.2) Patient currently connected to Extracorporeal Membrane Oxygenation at initiation of screening. 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 Use of investigational COVID-19 agents or any other investigational agents within 30 days prior to the first dose.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized, double-blinded, placebo-controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Normal saline 100 mL | Other: Intravenous normal saline<br>* Placebo<br>|
| Experimental: Experimental Dose<br>Normal saline 85 mL and ExoFlo 15 mL | Biological: ExoFlo<br>* Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ExoFlo, Extracellular Vesicles, Exosome, ARDS