Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS

Phase 2

Completed

Conditions: COVID-19
ARDS

Interventions: Biological: ExoFlo
Other: Intravenous normal saline

Registration Number: NCT04493242

Lead Sponsor: Direct Biologics, LLC

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 102

Inclusion Criteria

Provision of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy).
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 18-85.
COVID-19 positive as defined by positive Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) SARS-CoV-2.
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.
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.
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

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 five years.
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.
Active tuberculosis or cystic fibrosis.
Severe chronic respiratory disease including chronic obstructive pulmonary disease or pulmonary fibrosis requiring home oxygen > 5L/min.
Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
Pre-existing pulmonary hypertension.
Severe pre-existing hepatic impairment (presence of cirrhosis, liver function tests (LFTs) ≥ 6x baseline, INR ≥ 2.0).
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)
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).
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).
Patients who are not full code.
Endotracheal intubation duration ≤ 24 hours.
Moribund-expected survival < 24 hours.
Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH < 7.3)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Dose 2	ExoFlo	Normal saline 85 mL and ExoFlo 15 mL
Experimental Dose 1	ExoFlo	Normal saline 90 mL and ExoFlo 10 mL
Placebo	Intravenous normal saline	Normal saline 100 mL

Primary Outcome Measures

Name	Time	Method
Evaluation of 60-day Mortality Rate	60 days	To evaluate the 60-day mortality rate for IP 15mL as a treatment for COVID-19 associated moderate to severe ARDS compared to placebo. Reducing the mortality rate for hospitalized patients with COVID-19 associated ARDS is a measure of the treatment effect.

Secondary Outcome Measures

Name	Time	Method
Ventilation Free Days	Within 60 days of follow-up	Number of days for which patients are not on mechanical ventilation.
Incidence of Treatment Emergent Serious Adverse Events	61 days	Safety comparison performed between IP 15 mL and placebo arms
Overall Survival Rates	Days 15, 30, 60	Reducing the mortality rate for hospitalized patients with COVID-19 associated ARDS is a measure of the treatment effect.
Proportion of Discharged Patients	Days 7, 30, 60	Discharge is an unbiased measure of overall clinical improvement.
Time to Discharge	Number of days from the date of randomization until documented discharge from hospital, up to 60 days.	Discharge is an unbiased measure of overall clinical improvement.