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Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS (EXIT-COVID19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04493242
Recruitment Status : Completed
First Posted : July 30, 2020
Last Update Posted : January 14, 2022
Information provided by (Responsible Party):
Vikram Sengupta, 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.

Condition or disease Intervention/treatment Phase
Covid19 ARDS Pneumonia, Viral Biological: DB-001 Other: Intravenous normal saline Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:
EXIT COVID-19 is a FDA-approved, phase II double-blinded, placebo-controlled randomized controlled trial that enrolled 120 patients admitted with COVID-19 associated moderate-to-severe ARDS across up to 15 hospital sites in the United States.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-blinded
Primary Purpose: Treatment
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
Actual Study Start Date : September 24, 2020
Actual Primary Completion Date : May 1, 2021
Actual Study Completion Date : May 22, 2021

Arm Intervention/treatment
Placebo Comparator: Placebo
Normal saline 100 mL
Other: Intravenous normal saline

Experimental: Experimental Dose 1
Normal saline 90 mL and ExoFlo 10 mL, which is 800 Billion Extracellular Vesicles.
Biological: DB-001
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

Experimental: Experimental Dose 2
Normal saline 85 mL and ExoFlo 15 mL, which is 1.2 Trillion Extracellular Vesicles.
Biological: DB-001
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

Primary Outcome Measures :
  1. 7 Day Change in Partial Pressure of Arterial Oxygen to Fraction of Inspired Oxygen Ratio [ Time Frame: 61 days ]
    Efficacy Endpoint; PaO2/FiO2 ratio

Secondary Outcome Measures :
  1. Time to Recovery [ Time Frame: 61 days ]
    The number of days from the first study treatment until return of oxygenation saturation (SpO2) ≥ 93% on room air (or PaO2/FiO2 ≥ 300 mmHg). If patient has chronic lung disease, recovery is defined as pre-COVID-19 SpO2 and O2 support.

  2. Incidence of Serious Adverse Events (SAE) [ Time Frame: 61 days ]
    Safety Endpoint

  3. Number of Patients with All-cause Mortality [ Time Frame: 61 days ]
    Efficacy Endpoint

Other Outcome Measures:
  1. Serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) Level [ Time Frame: Days = 1, 4, 7, 10, 15, 29 *Labs are not drawn after hospitalization. ]

  2. CRP, D-dimer, Ferritin, IL-6, TNF-α [ Time Frame: Days = 1, 4, 7, 10, 15, 29 *Labs are not drawn after hospitalization ]
    Acute Phase Reactants

  3. Absolute Neutrophil Count (ANC), CD3+, CD4+, and CD8+ T Cells, NK Cells [ Time Frame: Days = 1, 4, 7, 10, 15, 29 *Labs are not drawn after hospitalization. ]
    Immune Cell Counts

  4. Sequential Organ Failure Assessment (SOFA) [ Time Frame: Days = 1, 15, 29 *Labs are only drawn if patient is still hospitalized. ]
    Mortality Prediction Score Ranging from 0 to 24 with Higher SOFA Score Correlating with Higher Mortality

  5. EQ-5D-5L Description Part Only, Which Includes 5 Dimensions of Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety Depression) [ Time Frame: Days = 15, 29, and 61 *Only Assessed for Outpatients ]
    Standardized Quality of Life Metric Where Each Dimension Is Assessed via 5 Levels; 5 Levels for Each Digit is Combined into a 5 Digit Descriptor.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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.
  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 sequalae 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04493242

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United States, Alabama
Helen Keller Hospital
Sheffield, Alabama, United States, 35660
United States, California
St. Joseph Hospital Heritage
Fullerton, California, United States, 92835
United States, Pennsylvania
Donald Guthrie Foundation/ Robert Packer Hospital
Sayre, Pennsylvania, United States, 18810
United States, Texas
Covenant Health
Lubbock, Texas, United States, 79410
PRX Research
Mesquite, Texas, United States, 75149
Sponsors and Collaborators
Direct Biologics, LLC
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Study Chair: Vikram Sengupta, MD Chief Medical Officer
Additional Information:
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Responsible Party: Vikram Sengupta, Principal Investigator, Direct Biologics, LLC
ClinicalTrials.gov Identifier: NCT04493242    
Other Study ID Numbers: DB-EF-PHASEII-001
First Posted: July 30, 2020    Key Record Dates
Last Update Posted: January 14, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vikram Sengupta, Direct Biologics, LLC:
extracellular vesicles
Additional relevant MeSH terms:
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Pneumonia, Viral
Respiratory Tract Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases