Study of Intravenous Administration of Allogeneic Adipose-Derived Mesenchymal Stem Cells for COVID-19-Induced Acute Respiratory Distress

Study Overview
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Brief Summary
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This is a Phase 2, randomized controlled, multicenter study to assess the safety and efficacy of COVI-MSC in the setting of current standard of care (SOC) treatments for COVID-19 infection in hospitalized subjects with ARD/ARDS.

Official Title
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Treatment of COVID-19-Induced Acute Respiratory Distress: A Phase 2 Study of Intravenous Administration of Allogeneic Adipose-Derived Mesenchymal Stem Cells

Conditions
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Covid19, ARDS

Intervention / Treatment
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* Drug: COVI-MSC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provides informed consent Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen 3. Is hospitalized with COVID-19-induced ARD or ARDS (any severity) with a PaO2/FiO2 ≤300. The PaO2/FiO2 may be estimated from pulse oximetry or determined by arterial blood gas Requires oxygen supplementation at screening Is willing to follow contraception requirements Exclusion Criteria: Current standard of care treatments for COVID-19 appear to be working and the subject is clinically improving A previous MSC infusion unrelated to this trial Have any of the following medical conditions: Cardio-pulmonary resuscitation within 14 days of randomization Uncontrolled or untreated symptomatic arrhythmias. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening may enroll Myocardial infarction within the last 6 weeks Congestive heart failure (NYHA Grade 3 or 4) Pulmonary hypertension (WHO Class III/IV) Currently receiving extracorporeal life support or membrane oxygenation (ECLS/ECMO) Alanine aminotransferase (ALT) ≥ 5x upper limit of normal (ULN) Relevant renal impairment (eGFR < 50 mL/min) Any significant medical condition, laboratory abnormality or psychiatric illness that in the investigator's opinion would interfere or prevent the subject from safely participating in the study Pregnant or breast feeding or planning for either during the study Suspected uncontrolled active bacterial, fungal, viral, or other infection (aside from infection with COVID-19) History of a splenectomy, lung transplant or lung lobectomy; Concurrent participation in another clinical trial involving therapeutic interventions (observational study participation is acceptable). Expected survival or time to withdrawal of life-sustaining treatments expected to be < 7 days. Do Not Intubate order; Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for continuous positive airway pressure or bi-level positive airway pressure (CPAP/BIPAP) used solely for sleep-disordered breathing

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVI-MSC<br>Allogeneic culture-expanded adipose-derived mesenchymal stem cells (MSCs) | Drug: COVI-MSC<br>* 1 x 10^6 MSCs/kg or 1.5 x 10^6 MSCs/kg, depending on CRP level<br>|
| Placebo Comparator: Placebo<br>Excipient | Drug: Placebo<br>* Equivalent volume of placebo will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at Day 28 | All-cause mortality at Day 28 | Randomization through Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at Days 60 and 90 | All-cause mortality at Days 60 and 90 | Randomization through Day 60 and Day 90 | 
| Number of ventilator-free days | Number of ventilator-free days through Day 28 | Randomization through Day 28 | 
| Improvement in oxygenation | Improvement in oxygenation at Day 2, 4, 6, 14, and 28 compared to Baseline, as assessed by PaO2/FiO2 | Randomization to Day 2, Day 4, Day 6, Day 14, Day 28 | 
| SOFA score at Day 28 | SOFA score at Day 28 compared to Baseline | Randomization to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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covid-19, ARDS