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

NCT04798716 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 020582
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Covid19; Novel Coronavirus Pneumonia; Acute Respiratory Distress Syndrome

Keywords

Novel Corona Virus Pneumonia; Exosomes; MSC; Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  90 Days

Secondary Outcomes (2)

• Analyze and report organ failure, associated with ICU mortality in participants confirmed with SARS-CoV2 infection, receiving ARDOXSO™ as an interventional exosome therapy.

  90 Days from last dose

• Record and analyze respiratory measures (Berlin Score/PEEP) following treatment regime.

  90 Days from last dose

Study Arms (4)

Escalating Dose First Cohort

EXPERIMENTAL

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 Second Cohort

EXPERIMENTAL

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 Third Cohort

EXPERIMENTAL

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)

Treatment Dose Fourth Cohort Randomized control ratio 1:3

PLACEBO COMPARATOR

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)

Interventions

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

Escalating dose 2 X 10\^9, 4 X 10\^9, 8 X 10\^9/mL

Also known as: Ardoxso

Escalating Dose First Cohort

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

Escalating dose 8 X 10\^9, 4 X 10\^9, 8 X 10\^9 mL

Also known as: Ardoxso

Escalating Dose Second Cohort

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

Dosed 8 X 10\^9, 8 X 10\^9, 8 X 10\^9 mL

Also known as: Ardoxso

Escalating Dose Third Cohort; Treatment Dose Fourth Cohort Randomized control ratio 1:3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• AVEM HealthCare: lead

Study Sites (1)

Mission Community Hospital

Panorama City, California, 91402, United States

Location

Related Publications (18)

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MeSH Terms

Conditions

COVID-19; Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Central Study Contacts

Tammy C Luttrell, PhD

CONTACT

833-957-0079; tammy.luttrell@avemhealthcare.com

Sant P Chawla, MD

CONTACT

santchawla@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Open-label for the first 15 patients treated in dose escalation. The final 40 participants are included in RCT. Double; participant and physician are masked.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Nested Cohort with Escalating Dose. The trial has three cohorts of 5 patients each. The subsequent cohort will receive an escalating dose of exosomes via intravenous infusion. The final group of 40 participants will be randomized 1:3 (placebo:intervention).

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 15, 2021
• Study Start: September 1, 2023
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 11, 2022

Record last verified: 2022-03

Locations

US (1)