Official Title
Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment: Expanded Access Protocol for Patients With COVID-19 Associated ARDS
Brief Summary

ExoFlo, Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Allograft Product, Infusion Treatment is currently being studied in Protocol DB-EF-PhaseIII-0001 in patients COVID-19 associated moderate to severe acute respiratory distress syndrome (ARDS). This expanded access protocol is an open label study intended to provide ExoFlo to critically ill patients who do not qualify for the Phase III randomized controlled trial (RCT) because they - Do not meet phase III eligibility criteria at current phase III sites. - Do meet phase III eligibility criteria but cannot access phase III sites. - Do not meet phase III eligibility criteria & cannot access phase III sites.

Detailed Description

Objectives:

First, to provide Investigational Medicinal Product (IMP) to patients with COVID-19
associated moderate to severe ARDS who do not qualify for Protocol DB-EF-PHASEIII-0001.
Secondarily, to collect safety and efficacy data.

Endpoints:

Primary Endpoint:

1) 60-day All-Cause Mortality

Secondary Endpoints:

1. Incidence of serious adverse events (SAEs).

2. Ventilator-free days (VFDs).

3. Time to discharge.

Exploratory Endpoints:

1. Acute phase reactants: C-reactive protein (CRP), D-dimer, and Ferritin change from
Baseline on Days 3, 5, 7, 10, 15, and 29 for subjects who are still hospitalized.

2. Sequential Organ Failure Assessment (SOFA) Score change from Baseline on Days 15, and 29
for subjects who are still hospitalized.

3. Improvement in partial pressure of arterial oxygen to fraction of inspired oxygen
(PaO2/FiO2) ratio from pre-infusion baseline (Day 0) to Day 7. PaO2 may be calculated
from arterial blood gas (ABG) or imputed from the SpO2 daily.

Number of subjects: ≤200

Phase: Phase II /Expanded Access Protocol for Intermediate Population

Available
Intermediate-size Population
COVID19
ARDS
Hypoxia
Cytokine Storm

Biological: ExoFlo

Intravenous administration of bone marrow mesenchymal stem cell derived extracellular vesicles

Eligibility Criteria

Inclusion Criteria:

1. Provision of informed consent by self or proxy.

2. Stated willingness to comply with study protocol.

3. Male or female of any age ≥ 18 years of age

4. May be pregnant unless the patient has one or more conditions listed under Exclusion
Criteria #3.

5. Positive Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) SARS-CoV-2.

6. Moderate to severe ARDS as defined by timing within ten days of known clinical insult
or new or worsening respiratory symptoms, bilateral opacities not fully explained by
effusions or lung collapse, and respiratory failure not fully explained by cardiac
failure or fluid overload, minimum 5 cm H2O PEEP on mechanical ventilation, and
PaO2/FiO2 ≤ 200 mmHg (if using an estimated P/F ratio, a S/F ≤ 235 is accepted).

7. Acute presentation of hypoxic respiratory failure requiring noninvasive oxygen support
OR mechanical ventilation (MV).

Exclusion Criteria:

1. Active malignancy requiring treatment within the last two years, with the exception of
non-melanoma skin cancers.

2. Patients who are not full code.

3. Pregnant patients with current or past history of eclampsia, preeclampsia, hemolysis,
elevated liver enzymes, or low platelet count (HELLP) syndrome during pregnancy.

4. New York Heart Association (NYHA) Functional Class III (symptoms present during
ordinary activities) or IV Heart Failure (symptoms present at rest) or listed for
heart transplant.

5. Chronic Kidney Disease (CKD) Stage IV (GFR 15-29 mL/min/1.73m2) and Stage V (GFR < 15
mL/min/1.73m2) or listed for kidney transplant.

6. Hepatic Impairment with Model for End-Stage Liver Disease (MELD) score ≥ 30 or listed
for liver transplant.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Contacts

Bill Arana
1-800-791-1021
clinicalaffairs@directbiologics.com

Bill Arana, Study Director
Direct Biologics, LLC

Direct Biologics, LLC
NCT Number
Keywords
Covid-19
ARDS
SARS-CoV-2
MeSH Terms
COVID-19
Hypoxia
Cytokine Release Syndrome