Official Title
Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19 Positive Patients With Acute Respiratory Distress Syndrome and/or Novel Coronavirus Pneumonia
Brief Summary

Novel coronavirus pneumonia (NCP) and acute respiratory distress syndrome (ARDS) are bothassociated with the prevailing upper respiratory tract infections caused by theRNA-containing SARS-CoV2 virus of the genius Betacoronavirus of the Coronaviridae family.As both the viral infiltration and infection progress, the host immune system responsecan be one of a rapidly developing fatal cytokine storm. In the ARDS or NCP ensuingprogression, the patient often succumbs to the effects of the hyper pro-inflammatoryresponse, hence contributing to the associated increased mortality as a result of thecytokine storm and associated pathogenesis.

Detailed Description

In December of 2019, in Wuhan, China, a novel coronavirus outbreak began. Globally this
disease referred to as COVID-19, is the result of a novel SARS-CoV2 virus which
predominantly targets Type II lung alveolar cells (AT2). The hyper response of the host
immune system can rapidly evolve into a life-threatening cytokine-release syndrome or
cytokine storm. The cytokine storm can predispose the patient to ARDS and/or NCP., or
both. Left unchecked, the ARDS pathogenesis rapidly culminates in disruption of cell
cytotoxicity mechanisms, excessive activation of cytotoxic lymphocytes, and a
predominance of type I (M1) macrophage; resulting in the massive release of a host of
proinflammatory cytokines (FNO-α, IL-1, IL-2, IL-6, IL-8, IL-10), granulocytic
colony-stimulating factor, monocytic chemoattractive protein 1. The result systemically
is a rise in surrogate inflammatory markers (C Reactive Protein, serum ferritin), with a
corresponding infiltration of internal organs and tissues by activated macrophage,
T-lymphocytes and a predominance of cellular apoptosis. The resulting hyperinflammatory
pathogenic reaction may result in severe aveolar lesions leading to death, scarring, or
severe lung damage, persisting well after discharge.

Experimental studies have demonstrated that mesenchymal stem cells (MSCs) and MSC-culutre
media (MSC-CM) may significantly reduce the pro-inflammatory bias and associated
pathologic impairment resulting. The MSC-CM, known to contain exosomes, has been shown to
have an anti-inflammatory effect. Further exosomes associated with the amniotic membrane,
long used in the treatment of burn and wounds, have been show to have a regenerative
effect.

The purpose of this protocol is to explore the safety and efficacy of an intravenous
injection of MSC derived exosomes in the treatment of severe patients (moderate to severe
Berlin score) with ARDS or NCP.

Unknown status
COVID19
Novel Coronavirus Pneumonia
Acute Respiratory Distress Syndrome

Drug: MSC-exosomes delivered intravenously every other day on an escalating dose: (2:4:8)

Escalating dose 2 X 10^9, 4 X 10^9, 8 X 10^9/mL
Other Name: Ardoxso

Drug: MSC-exosomes delivered intravenously every other day on an escalating dose (8:4:8)

Escalating dose 8 X 10^9, 4 X 10^9, 8 X 10^9 mL
Other Name: Ardoxso

Drug: MSC-exosomes delivered intravenously every other day (8:8:8)

Dosed 8 X 10^9, 8 X 10^9, 8 X 10^9 mL
Other Name: Ardoxso

Eligibility Criteria

Inclusion Criteria:

- Informed Consent given

- Male and female patients age 18 years or older

- Patients with coronavirus (SARS-CoV-2) infection confirmed prior to enrollment by
any test with local regulatory approval

- Patients who require intensive care as determined by the following objective
criteria:

- Respiratory rate>25/minute

- Oxygen saturation <93% on room air; or the

- Use of high flow oxygen by nasal cannula at a rate ≥ 4L/minute.

- Patients with lung imaging demonstrating bilateral or diffuse pulmonary infiltrates
on chest X-ray or CT scan.

- Patients with moderate to severe ARDS as defined by Berlin Criteria

- Patients who require invasive mechanical ventilation (IMV)

Exclusion Criteria:

- Patients will be excluded from the study if ONE of the following applies:

- History of hypersensitivity to any drugs of similar classes to exosomes

- Suspected active uncontrolled bacterial, fungal, or viral (besides SARS-CoV-2)
infection

- Currently receiving ECMO, nitric oxide therapy, or high-frequency oscillatory
ventilation

- In the option of the investigator, the patient is unlikely to survive for more
than 24 hours post-enrollment

- Patients who are on long-term use of select oral or injectable anti-rejection
or immunomodulatory drugs

- Pregnant or nursing (lacking) women

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
United States
Locations

Mission Community Hospital
Panorama City, California, United States

Investigator: Sant P Chawla, MD

Contacts

Tammy C Luttrell, PhD
833-957-0079
tammy.luttrell@avemhealthcare.com

Sant P Chawla, MD
santchawla@gmail.com

Not Provided

AVEM HealthCare
NCT Number
Keywords
Novel Corona Virus Pneumonia
Exosomes
MSC
Acute Respiratory Distress Syndrome
MeSH Terms
COVID-19
Pneumonia
Coronavirus Infections
Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Syndrome