Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial

Study Overview
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Brief Summary
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This is a Phase 2 multicenter randomized (2:1), placebo-controlled trial to evaluate early signs of efficacy of allogeneic, umbilical cord-derived (UC) mesenchymal stromal cells (MSCs) in patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS). Randomized participants (N=54) will receive 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) or blinded placebo. The MSC product will be provided as 2.5 million cells/ml suspended in PlasmaLyte A containing 5% Human Albumin. The appearance-matched placebo product contains the same excipients, PlasmaLyte A and 5% Human Albumin, as the UC-MSCs.

Official Title
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Cellular Immuno-Therapy for COVID-19 ARDS Randomized Clinical Trial

Conditions
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Covid19, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Biological: UC-MSCs
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of ≥18 years Laboratory-confirmed SARS-CoV-2 infection during the current admission On invasive, non-invasive mechanical ventilation (NIV) (PEEP ≥5 cmH20) or high-flow nasal canula (HFNC) oxygen therapy (minimum total flow rate of 40 lpm) ARDS (onset <96h) as per the international consensus definition (P/F ratio < 300 with PEEP ≥5cm H20 or on HFNC), not due primarily to cardiac causes. Exclusion Criteria: No consent/inability to obtain consent Rockwood Clinical Frailty Score > 4 Moribund patient not expected to survive 24 hours Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50% Currently receiving extracorporeal life support Pregnant or lactating Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial Moderate to severe chronic liver disease (Childs-Pugh Score > 12) Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen Documented deep venous thrombosis or pulmonary embolism within the preceding 3 months Inability/contra-indications to receiving local standard of care thromboprophylaxis Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months) Known HIV, Hep B/C positive, or active tuberculosis Multisystem shock (SOFA score change from baseline of >2 in >2 systems) Patient, surrogate, or physician not committed to full support including intubation (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized (2:1) placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSCs Arm<br>3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) | Biological: UC-MSCs<br>* 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs)<br>|
| Placebo Comparator: Placebo Arm<br>3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) | Biological: Placebo<br>* PlasmaLyte A and 5% Human Albumin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days free of oxygen by NIV/HFNC or mechanical ventilation at Day 28 |  | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers of systemic inflammatory response | Interleukin levels change from Baseline to 24 hours after each MSC infusion | Change from Baseline to 24 hours after each MSC infusion | 
| Biomarkers of endothelial function | Angiopoietin levels change from Baseline to 24 hours after each MSC infusion | Change from Baseline to 24 hours after each MSC infusion | 
| ICU mortality | Number of deaths at day 28 | Day 28 |