Acute Respiratory Distress Syndrome, ARDS
Conditions
Keywords
ExoFlo, Extracellular Vesicles, Exosome, ARDS
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).
Interventions
BIOLOGICALExoFlo
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles
Placebo
Sponsors
Direct Biologics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-Blinded
Intervention model description
Multicenter, randomized, double-blinded, placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Time to death | 60 days | Reducing the mortality rate for hospitalized patients moderate-to-severe ARDS is a measure of the treatment effect. |
Countries
United States
Contacts
CONTACTBill Arana
STUDY_DIRECTORBill Arana
Direct Biologics, LLC
Outcome results
None listed