The Use of Exosomes for the Treatment of Acute Respiratory Distress Syndrome or Novel Coronavirus Pneumonia Caused by COVID-19 (ARDOXSO)

March 10, 2022 updated by: AVEM HealthCare

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

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

55

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Panorama City, California, United States, 91402
        • Mission Community Hospital
        • Contact:
          • Sant P Chawla, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Escalating Dose First Cohort

First Cohort:

Five patients will receive an escalating dose every other day for a period of 5 days, with a minimum of 24 hours between doses recorded. Dose escalation will begin at 2 x 10^9 exosomes
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 Names:
  • Ardoxso
Experimental: Escalating Dose Second Cohort

Second Cohort:

Five patients will receive an escalating dose every other day for a period of 5 days, with a minimum of 24 hours between doses recorded. Dose escalation will begin at 4 x 10^9 exosomes.
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 Names:
  • Ardoxso
Experimental: Escalating Dose Third Cohort
Five patients will receive a treatment dose of 8 X 10^9 exosomes every other day for a period of 5 days, with a minimum of 24 hours between doses recorded.
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 Names:
  • Ardoxso
Placebo Comparator: Treatment Dose Fourth Cohort Randomized control ratio 1:3

Fourth Cohort:

Randomized Cohort Up to 40 patients may be enrolled in this phase of the trial. For those receiving the placebo (~25%), 3 doses will be given over the 5 day period, dispensed from identical vials with physician and patient blinded. The full dose of 8 X 10^9 exosomes will be given to 75% of the patients in 3 doses over the course of 5 days, with one dose occurring every other day.
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 Names:
  • Ardoxso

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure and report the number of participants with treatment-related-adverse events as assessed by CTCAE v4.0; for patients receiving ARDOXSO™, perinatal MSC-derived exosome therapy.
Time Frame: 90 Days
Quantify safety of ARDOXSO™, an interventional exosome therapy in COVID-19 in participants confirmed with SARS-CoV-2 infection who receive ARDOXSO™ as an intervention.
90 Days
Tabulate and report the number of IMV days for patients receiving ARDOXSO™ perinatal MSC-derived exosome therapy.
Time Frame: 90 Days
Quantify efficacy of ARDOXSO™, an interventional exosome therapy in COVID-19 in participants confirmed with SARS-CoV-2 infection who receive ARDOXSO™ as an intervention.
90 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analyze and report organ failure, associated with ICU mortality in participants confirmed with SARS-CoV2 infection, receiving ARDOXSO™ as an interventional exosome therapy.
Time Frame: 90 Days from last dose
Correlate and analyze the Sequential Organ Failure Assessment (SOFA) score in participants confirmed with SARS-CoV2 infection, receiving ARDOXSO™, an interventional exosome therapy in COVID-19 patients. An increased SOFA score is predictive of increased mortality.
90 Days from last dose
Record and analyze respiratory measures (Berlin Score/PEEP) following treatment regime.
Time Frame: 90 Days from last dose
Berlin Score is a validated measure of Acute Respiratory Distress Syndrome diagnosis, which is common in COVID-19 patients, before and after receiving the interventional exosome therapy, ARDOXSO™.
90 Days from last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AVEM HealthCare

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2023

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

March 12, 2021

First Submitted That Met QC Criteria

March 12, 2021

First Posted (Actual)

March 15, 2021

Study Record Updates

Last Update Posted (Actual)

March 11, 2022

Last Update Submitted That Met QC Criteria

March 10, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 020582

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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