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

Sponsor
Direct Biologics, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT04493242
Collaborator
(none)
120
5
3
7.9
24
3

Study Details

Study Description

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
  • Biological: DB-001
  • Other: Intravenous normal saline
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Multi-center, double-blinded, placebo-controlled, randomized controlled trial.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 :
Sep 24, 2020
Actual Primary Completion Date :
May 1, 2021
Actual Study Completion Date :
May 22, 2021

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Normal saline 100 mL

Other: Intravenous normal saline
Placebo

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

Outcome Measures

Primary Outcome Measures

  1. 7 Day Change in Partial Pressure of Arterial Oxygen to Fraction of Inspired Oxygen Ratio [61 days]

    Efficacy Endpoint; PaO2/FiO2 ratio

Secondary Outcome Measures

  1. Time to Recovery [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) [61 days]

    Safety Endpoint

  3. Number of Patients with All-cause Mortality [61 days]

    Efficacy Endpoint

Other Outcome Measures

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

    Viremia

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

    Immune Cell Counts

  4. Sequential Organ Failure Assessment (SOFA) [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 85 Years
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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Helen Keller Hospital Sheffield Alabama United States 35660
2 St. Joseph Hospital Heritage Fullerton California United States 92835
3 Donald Guthrie Foundation/ Robert Packer Hospital Sayre Pennsylvania United States 18810
4 Covenant Health Lubbock Texas United States 79410
5 PRX Research Mesquite Texas United States 75149

Sponsors and Collaborators

  • Direct Biologics, LLC

Investigators

  • Study Chair: Vikram Sengupta, MD, Chief Medical Officer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
Vikram Sengupta, Principal Investigator, Direct Biologics, LLC
ClinicalTrials.gov Identifier:
NCT04493242
Other Study ID Numbers:
  • DB-EF-PHASEII-001
First Posted:
Jul 30, 2020
Last Update Posted:
Jan 14, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Vikram Sengupta, Principal Investigator, Direct Biologics, LLC
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 14, 2022