A Phase 1/2 interventional study of MSC-exosomes delivered intravenously every other day on an escalating dose: (2:4:8) and MSC-exosomes delivered intravenously every other day on an escalating dose (8:4:8) in Covid19, Novel Coronavirus Pneumonia and Acute Respiratory Distress Syndrome, sponsored by AVEM HealthCare. Status unknown at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-11.
Sponsored by AVEM HealthCare · Phase 1/2, Interventional, and Treatment
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.
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.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's planned enrollment of 55 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →This is the only study on the registry with AVEM HealthCare as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Patients who require intensive care as determined by the following objective criteria:
Exclusion Criteria:
Patients will be excluded from the study if ONE of the following applies:
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)
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)
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)
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)
Escalating dose 2 X 10\^9, 4 X 10\^9, 8 X 10\^9/mL
Also known as: Ardoxso
Escalating dose 8 X 10\^9, 4 X 10\^9, 8 X 10\^9 mL
Also known as: Ardoxso
Dosed 8 X 10\^9, 8 X 10\^9, 8 X 10\^9 mL
Also known as: Ardoxso
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.
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.
Time frame: 90 Days
Tabulate and report the number of IMV days for patients receiving ARDOXSO™ perinatal MSC-derived exosome therapy.
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.
Time frame: 90 Days
Analyze and report organ failure, associated with ICU mortality in participants confirmed with SARS-CoV2 infection, receiving ARDOXSO™ as an interventional exosome therapy.
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.
Time frame: 90 Days from last dose
Record and analyze respiratory measures (Berlin Score/PEEP) following treatment regime.
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™.
Time frame: 90 Days from last dose
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