We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Bone Marrow Mesenchymal Stem Cell Derived EVs for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05354141
Recruitment Status : Recruiting
First Posted : April 29, 2022
Last Update Posted : August 30, 2022
Sponsor:
Information provided by (Responsible Party):
Direct Biologics, LLC

Tracking Information
First Submitted Date  ICMJE April 27, 2022
First Posted Date  ICMJE April 29, 2022
Last Update Posted Date August 30, 2022
Actual Study Start Date  ICMJE July 1, 2022
Estimated Primary Completion Date April 3, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2022)
The primary efficacy endpoint is overall 60-day mortality (due to any cause). [ Time Frame: 60 days ]
The primary efficacy endpoint is overall 60-day mortality (due to any cause).
Original Primary Outcome Measures  ICMJE
 (submitted: April 27, 2022)
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Related Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial. [ Time Frame: 60 days ]
To evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EVs), ExoFlo, versus placebo as early goal directed therapy for moderate-to-severe acute respiratory distress syndrome (ARDS) caused by COVID-19.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bone Marrow Mesenchymal Stem Cell Derived EVs for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial
Official Title  ICMJE Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS):
Brief Summary Extracellular Vesicle Infusion as Early Goal Directed Therapy for COVID-19 related ARDS (EXTINGuish COVID-19) is a multicenter, double-blinded, placebo-controlled, randomized clinical trial to evaluate the efficacy of ExoFlo in treating moderate to severe ARDS caused by COVID-19.
Detailed Description

The purpose of the trial is to evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EVs), ExoFlo, versus placebo as treatment for COVID-19 associated moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

The study population includes 610 male and female patients between 18 and 85 years of age hospitalized with COVID-19 associated ARDS.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE COVID-19 Acute Respiratory Distress Syndrome
Intervention  ICMJE Drug: EXOFLO
The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less. The intervention will be infused over 60 minutes on Day 1 and repeated on Day 4 provided that the patient has not recovered as defined by WHO ordinal scale category 4 or less.
Study Arms  ICMJE
  • Placebo Comparator: Treatment Arm 1
    PLACEBO Normal saline 100 mL
    Intervention: Drug: EXOFLO
  • Experimental: Treatment Arm 2
    IP (ExoFlo) 15ml dose in Normal saline 85 mL, which is approximately 1.2 trillion EVs.
    Intervention: Drug: EXOFLO
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 27, 2022)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 3, 2023
Estimated Primary Completion Date April 3, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  1. Admitted to hospital with symptoms suggestive of COVID-19 infection.
  2. Subject (or legally authorized representative) provides informed consent prior to the initiation of any study procedures.
  3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
  4. Male or nonpregnant female aged 18-85 of age at time of enrollment.
  5. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from time of screening through Day 61.
  6. Meets criteria for either severe or critical COVID-19 as evidenced by

    a. Severe COVID-19:

    i. SARS-CoV-2 PCR positive in sample collected within one week prior to randomization ii. Severe symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress iii. Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥ 30 per minute, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air at sea level

    b. Critical COVID-19:

    i. SARS-CoV-2 PCR positive in sample collected within one week prior to randomization

    ii. Evidence of critical illness, defined by at least one of the following:

    • Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation, oxygen delivery by high flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5), oxygen delivery by high flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure (i.e. clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation).
    • Shock (defined by systolic blood pressure < 90 mmHg, or diastolic blood pressure 60 mmHg or requiring pressors)
    • Multi-organ dysfunction/failure
  7. PaO2/FiO2 (P/F ratio) ≤ 200.

Note for Inclusion Criterion #7:

  • PaO2 will be obtained from ABG.
  • FiO2 may be obtained from the setting on MV, CPAP, BIPAP, HFNO, or HFOV. If the patient is on RA, NC, FM, or NRB, Appendix Section 10.3 will be used for estimating FiO2 from oxygen delivery.

EXCLUSION CRITERIA:

  1. Active malignancy requiring treatment within the last five years.
  2. Any uncontrolled chronic respiratory disease, such as asthma or COPD.
  3. Use of extracorporeal membrane oxygenation (ECMO) during the current hospitalization.
  4. ALT or AST > 5 x Upper Limit of Normal (ULN).
  5. Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min.
  6. Overt Disseminated Intravascular Coagulopathy (DIC) as evidenced by a total score of ≥ 5 on the following DIC score from International Society of Thrombosis & Hemostasis:

    • INR ≤ 1.3 (0 Points); 1.3- 1.7 (1 Point); > 1.7 (2 Points)
    • Fibrinogen > 100 mg/dL (0 Points); < 100 mg/dL (1 Point)
    • D-dimer < 400 ng/dL (0 Points); 400-4000 ng/mL (2 Points); >4,000 ng/ml (3 Points)
    • Platelets > 100,000/uL (0 Points); 50,000-100,000/uL (1 Point); < 50,000/uL (2 Points)
  7. Pneumonia that is primarily attributable to a non-COVID-19 related process, including tuberculosis, mycoplasma, aspiration pneumonia or pneumonia that is exclusively bacterial, or originating from a diagnosed alternative virus (e.g., influenza).
  8. DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation.
  9. Endotracheal intubation duration > 48 hours.
  10. Moribund-expected survival < 24 hours.
  11. Severe metabolic disturbances on presentation (e.g., ketoacidosis, pH < 7.3)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Heidi Moran 800-791-1021 hmoran@directbioloics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05354141
Other Study ID Numbers  ICMJE DB-EF-PHASEIII-0001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Direct Biologics, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Direct Biologics, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Vikram Sengupta, MD Direct Biologics
PRS Account Direct Biologics, LLC
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP