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Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)

Primary Purpose

Acute Respiratory Distress Syndrome, ARDS

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
ExoFlo
Intravenous normal saline
Sponsored by
Direct Biologics, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring ExoFlo, Extracellular Vesicles, Exosome, ARDS

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Dignity Health Chandler Regional Medical CenterRecruiting
  • Providence St. Jude Medical Center
  • UC IrvineRecruiting
  • UC Davis Health
  • UC San FranciscoRecruiting
  • Ascension Via Christi HospitalRecruiting
  • Brigham and Women's HospitalRecruiting
  • Jackson Pulmonary Associates and Baptist Clinical Research InstituteRecruiting
  • Atrium Health Wake Forest BaptistRecruiting
  • University Hospitals Cleveland Medical CenterRecruiting
  • Guthrie Medical Group, PCRecruiting
  • Baylor University Medical CenterRecruiting
  • JPS Health NetworkRecruiting
  • Houston Methodist HospitalRecruiting
  • PRX Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Experimental Dose

Arm Description

Normal saline 100 mL

Normal saline 85 mL and ExoFlo 15 mL

Outcomes

Primary Outcome Measures

Evaluation of 60-day All-cause Mortality
To evaluate the 60-day mortality rate for IMP 15mL as a treatment for moderate-to-severe ARDS compared to placebo. Reducing the mortality rate for hospitalized patients with moderate-to-severe ARDS is a measure of the treatment effect.

Secondary Outcome Measures

Time to death
Reducing the mortality rate for hospitalized patients moderate-to-severe ARDS is a measure of the treatment effect.
Ventilator-free days (VFDs)
Number of days for which patients are not on mechanical ventilation.
Oxygen free days
Number of days for which patients are not on oxygen support.
ICU free days
Number of days for which patients are not in the ICU.
Incidence of Treatment Emergent Serious Adverse Events (TESAEs)
Safety comparison performed between IMP 15 mL and placebo arms

Full Information

First Posted
April 27, 2022
Last Updated
October 23, 2023
Sponsor
Direct Biologics, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05354141
Brief Title
Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)
Official Title
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles for Hospitalized Patients With Moderate-to-Severe ARDS: A Phase III Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
March 3, 2024 (Anticipated)
Study Completion Date
August 3, 2024 (Anticipated)

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 (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EVs), ExoFlo, versus placebo for the treatment of hospitalized patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).
Detailed Description
This is a Phase III, multicenter, randomized, double-blinded, placebo-controlled trial for the treatment of moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome, ARDS
Keywords
ExoFlo, Extracellular Vesicles, Exosome, ARDS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Multicenter, randomized, double-blinded, placebo-controlled trial
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double-Blinded
Allocation
Randomized
Enrollment
970 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal saline 100 mL
Arm Title
Experimental Dose
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 All-cause Mortality
Description
To evaluate the 60-day mortality rate for IMP 15mL as a treatment for moderate-to-severe ARDS compared to placebo. Reducing the mortality rate for hospitalized patients with moderate-to-severe ARDS is a measure of the treatment effect.
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Time to death
Description
Reducing the mortality rate for hospitalized patients moderate-to-severe ARDS is a measure of the treatment effect.
Time Frame
60 days
Title
Ventilator-free days (VFDs)
Description
Number of days for which patients are not on mechanical ventilation.
Time Frame
Day 29
Title
Oxygen free days
Description
Number of days for which patients are not on oxygen support.
Time Frame
Day 29
Title
ICU free days
Description
Number of days for which patients are not in the ICU.
Time Frame
Day 29
Title
Incidence of Treatment Emergent Serious Adverse Events (TESAEs)
Description
Safety comparison performed between IMP 15 mL and placebo arms
Time Frame
61 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women aged 18-75 years of age Presence of the following criteria for moderate to severe ARDS as defined by the Berlin Criteria within 24 hours of the first infustion: Onset within 7 days of known clinical insult or requiring increasing respiratory rate, increasing oxygen flows, or increased work of breathing, and Bilateral lung opacities not fully explained by pleural effusions, atelectasis, or nodules, and PaO2/FiO2 (P/F ratio) ≤ 200 mm Hg, and Invasive or noninvasive ventilation with a minimum PEEP 5 cm H2O or minimum of continuous positive airway pressure (CPAP) 5 cm H2O, or High Flow Nasal Oxygen at ≥ 30 L/min, and Respiratory failure not fully explained by cardiac failure or fluid overload. Exclusion Criteria: Lack of signed and dated informed consent form (either by the individual or by the individual's healthcare proxy). Stated unwillingness to comply with all study procedures and availability for the duration of the study 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 two years, with the exception of non-melanoma skin cancers. Major physical trauma in the last 2 days, including motor vehicle accidents, assaults, mechanical falls with sequelae of significant bleeding or craniofacial bruising, and surgeries, such that not one or more injury may be undiagnosed at time of screening. Duration of mechanical ventilation exceeds 3 days or 72 hours from diagnosis of ARDS. ALT or AST > 8 x Upper Limit of Normal (ULN). Documented history of cirrhosis. DNR order, as in electing not to receive chest compressions, cardiac defibrillation, cardiac drugs, or intubation. Moribund-expected survival < 24 hours. Severe metabolic disturbances at randomization (e.g., ketoacidosis, pH < 7.2) Patient currently connected to Extracorporeal Membrane Oxygenation at initiation of screening. If the candidate, either a male or female of reproductive potential, is unwilling to two methods 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 method OR maintenance of abstinence must include the time from the beginning of the screening period until Day 61, day of withdrawal or early termination Use of investigational COVID-19 agents or any other investigational agents within 30 days prior to the first dose.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amy Lightner, MD
Phone
512-354-7124
Email
alightner@directbioloics.com
First Name & Middle Initial & Last Name or Official Title & Degree
Stephanie Cahill
Email
scahill@directbiologics.com
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
Dignity Health Chandler Regional Medical Center
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristopher Roach, MD
Facility Name
Providence St. Jude Medical Center
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Park, MD
Facility Name
UC Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alpesh Amin, MD
Facility Name
UC Davis Health
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timothy Albertson, MD,MPH,Ph.D
Facility Name
UC San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael A Matthay, MD
Facility Name
Ascension Via Christi Hospital
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margaret Hagan, MD
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gyorgy Frendl, MD, PhD
Facility Name
Jackson Pulmonary Associates and Baptist Clinical Research Institute
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Rappai, MD
Facility Name
Atrium Health Wake Forest Baptist
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kevin W. Gibbs, MD
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenneth Remy, MD
Facility Name
Guthrie Medical Group, PC
City
Sayre
State/Province
Pennsylvania
ZIP/Postal Code
18840
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Walsh, MD
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Saman Ahmed, MD
Facility Name
JPS Health Network
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Pientka, MD
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eleftherios Mylonakis, MD
Facility Name
PRX Research
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75149
Country
United States
Individual Site Status
Active, not recruiting

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 Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)

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