Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS (EXIT-COVID19)
Primary Purpose
COVID-19, ARDS
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ExoFlo
Intravenous normal saline
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, ARDS, Extracellular Vesicles, Exosome
Eligibility Criteria
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 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.
- 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 sequalae 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)
Sites / Locations
- Helen Keller Hospital
- St. Joseph Heritage Healthcare
- Donald Guthrie Foundation/ Robert Packer Hospital
- Memorial Hermann Memorial City Medical Center
- Covenant Health System
- PRX Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Experimental Dose 1
Experimental Dose 2
Arm Description
Normal saline 100 mL
Normal saline 90 mL and ExoFlo 10 mL
Normal saline 85 mL and ExoFlo 15 mL
Outcomes
Primary Outcome Measures
Evaluation of 60-day Mortality Rate
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
Overall Survival Rates
Reducing the mortality rate for hospitalized patients with COVID-19 associated ARDS is a measure of the treatment effect.
Proportion of Discharged Patients
Discharge is an unbiased measure of overall clinical improvement.
Time to Discharge
Discharge is an unbiased measure of overall clinical improvement.
Incidence of Treatment Emergent Serious Adverse Events
Safety comparison performed between IP 15 mL and placebo arms
Ventilation Free Days
Number of days for which patients are not on mechanical ventilation.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04493242
Brief Title
Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS
Acronym
EXIT-COVID19
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
September 24, 2020 (Actual)
Primary Completion Date
May 1, 2021 (Actual)
Study Completion Date
May 22, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Direct Biologics, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, ARDS
Keywords
COVID-19, ARDS, Extracellular Vesicles, Exosome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Multi-center, double-blinded, placebo-controlled, randomized controlled trial.
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal saline 100 mL
Arm Title
Experimental Dose 1
Arm Type
Experimental
Arm Description
Normal saline 90 mL and ExoFlo 10 mL
Arm Title
Experimental Dose 2
Arm Type
Experimental
Arm Description
Normal saline 85 mL and ExoFlo 15 mL
Intervention Type
Biological
Intervention Name(s)
ExoFlo
Intervention Description
Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles
Intervention Type
Other
Intervention Name(s)
Intravenous normal saline
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Evaluation of 60-day Mortality Rate
Description
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.
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Overall Survival Rates
Description
Reducing the mortality rate for hospitalized patients with COVID-19 associated ARDS is a measure of the treatment effect.
Time Frame
Days 15, 30, 60
Title
Proportion of Discharged Patients
Description
Discharge is an unbiased measure of overall clinical improvement.
Time Frame
Days 7, 30, 60
Title
Time to Discharge
Description
Discharge is an unbiased measure of overall clinical improvement.
Time Frame
Number of days from the date of randomization until documented discharge from hospital, up to 60 days.
Title
Incidence of Treatment Emergent Serious Adverse Events
Description
Safety comparison performed between IP 15 mL and placebo arms
Time Frame
61 days
Title
Ventilation Free Days
Description
Number of days for which patients are not on mechanical ventilation.
Time Frame
Within 60 days of follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Lightner, MD
Organizational Affiliation
Direct Biologics, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Helen Keller Hospital
City
Sheffield
State/Province
Alabama
ZIP/Postal Code
35660
Country
United States
Facility Name
St. Joseph Heritage Healthcare
City
Anaheim
State/Province
California
ZIP/Postal Code
92805
Country
United States
Facility Name
Donald Guthrie Foundation/ Robert Packer Hospital
City
Sayre
State/Province
Pennsylvania
ZIP/Postal Code
18840
Country
United States
Facility Name
Memorial Hermann Memorial City Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
Covenant Health System
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
PRX Research
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75149
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://directbiologics.com/
Description
Direct Biologics, LLC
Learn more about this trial
Extracellular Vesicle Infusion Treatment for COVID-19 Associated ARDS
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