Clinical trial NCT04493242: Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS
Official title: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS): A Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
ARDS
Keywords: COVID-19
ARDS
Extracellular Vesicles
Exosome
Lead sponsor: Direct Biologics, LLC
Sponsor class: INDUSTRY
First posted: 2020-07-30
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of intravenous administration of bone marrow derived extracellular vesicles, ExoFlo, versus placebo as treatment for moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) in patients with severe COVID-19.

Detailed description: This is a Phase II, double-blinded, placebo-controlled, randomized controlled trial that enrolled 102 subjects that were admitted with COVID-19 associated moderate-to-severe ARDS across 6 sites in the United States.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 18-85.
4. COVID-19 positive as defined by positive Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) SARS-CoV-2.
5. Moderate to severe ARDS as defined by modified Berlin definition, \* which includes timing within 1 week of known clinical insult or new or worsening respiratory symptoms; bilateral opacities not fully explained by effusions, or lung collapse; respiratory failure not fully explained by cardiac failure or fluid overload; PaO2/FiO2 ≤ 200 mm Hg.

   \*Modified Berlin definition used in this study is the full Berlin definition, albeit without the PEEP specification, which implies mechanical ventilation.
6. Hypoxia requiring noninvasive oxygen support such as Nasal Cannula (NC), Nonrebreather (NRB), Bilevel Positive Airway Pressure (BIPAP), Continuous Positive Airway Pressure (CPAP), high flow nasal cannula oxygen (HFNC O2) or mechanical ventilation (MV) despite initiating standard of care.
7. If the candidate is either a male or female of reproductive potential, he or she must agree to use of double barrier method 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 barrier method OR maintenance of abstinence must include the time from the beginning of the screening period until 90 days following the last dose of the study treatment.

Exclusion Criteria:

1. Vulnerable populations such as pregnant patients, children, individuals with severe physical or mental disabilities who cannot provide meaningful consent.
2. Active malignancy requiring treatment within the last five years.
3. Major physical trauma in the last 5 days, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries.
4. Active tuberculosis or cystic fibrosis.
5. Severe chronic respiratory disease including chronic obstructive pulmonary disease or pulmonary fibrosis requiring home oxygen \> 5L/min.
6. Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
7. Pre-existing pulmonary hypertension.
8. Severe pre-existing hepatic impairment (presence of cirrhosis, liver function tests (LFTs) ≥ 6x baseline, INR ≥ 2.0).
9. Pre-existing Chronic Kidney Disease (CKD) stage IIIb or End Stage Renal Disease (ESRD) prior to onset of COVID-19 (stage I, II, and IIIa are acceptable)
10. Irreversible coagulopathy (e.g., frequently occluded vascular access despite anticoagulation, precipitous platelet drops concurrent with end-organ damage suggesting consumptive process) or irreversible bleeding disorder (e.g., frequent bleeding from vascular access, endotracheal tubes, and foley).
11. Pneumonia clearly attributable to a non-COVID-19 related process, including aspiration pneumonia or pneumonia that is exclusively bacterial, or originating from a diagnosed alternative virus (e.g., influenza).
12. Patients who are not full code.
13. Endotracheal intubation duration ≤ 24 hours.
14. Moribund-expected survival \< 24 hours.
15. Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH \< 7.3)

Primary outcomes:
measure: Evaluation of 60-day Mortality Rate
timeFrame: 60 days
Secondary outcomes:
measure: Overall Survival Rates
timeFrame: Days 15, 30, 60
measure: Proportion of Discharged Patients
timeFrame: Days 7, 30, 60
measure: Time to Discharge
timeFrame: Number of days from the date of randomization until documented discharge from hospital, up to 60 days.
measure: Incidence of Treatment Emergent Serious Adverse Events
timeFrame: 61 days
measure: Ventilation Free Days
timeFrame: Within 60 days of follow-up
Other outcomes:
Locations:
city: Sheffield
country: United States
facility: Direct Biologics Investigational Site
state: Alabama
city: Anaheim
country: United States
facility: Direct Biologics Investigational Site
state: California
city: Sayre
country: United States
facility: Direct Biologics Investigational Site
state: Pennsylvania
city: Houston
country: United States
facility: Direct Biologics Investigational Site
state: Texas
city: Lubbock
country: United States
facility: Direct Biologics Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Direct Biologics Investigational Site
state: Texas
Study officials:
affiliation: Direct Biologics, LLC
name: Bill Arana
role: STUDY_DIRECTOR
References: