Study of Allogeneic Adipose-Derived Mesenchymal Stem Cells for Treatment of COVID-19 Acute Respiratory Distress

Study Overview
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Brief Summary
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This is a Phase 2 study to assess COVI-MSC in the setting of current standard of care in hospitalized subjects with RT-PCR confirmed SARS-CoV-2 (COVID-19) infection and acute respiratory distress / acute respiratory distress syndrome.

Detailed Description
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This is a Phase 2 multicenter (United States and Mexico) study to assess the safety and preliminary efficacy of COVI-MSC in the setting of current standard of care in hospitalized subjects with RT-PCR confirmed SARS-CoV-2 (COVID-19) infection and acute respiratory stress (ARD) / acute respiratory distress syndrome (ARDS). Subjects will be randomized 1:1 COVI-MSC to placebo. COVI-MSC or placebo will be administered intravenously on Day 0, Day 2, and Day 4.

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

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Laboratory-confirmed SARS-CoV-2 infection as determined by an approved polymerase chain reaction (PCR) or an approved antigen test of any specimen (can be documented from inpatient medical record) Hospitalized with at least severe COVID-19-induced ARD or ARDS as defined per FDA Guidance; COVID-19: Developing Drugs and Biological Products for Treatment or Prevention Requires oxygen supplementation at Screening Willing to follow contraception guidelines Exclusion Criteria: Current standard of care treatments for COVID-19 appear to be working and the subject is clinically improving Has severe ARDS with a PaO2/FiO2 (PF ratio) ≤ 100 mmHg or SpO2/FiO2 ratio < 150 mmHg with PEEP ≥ 5cm H2O A previous stem cell infusion unrelated to this trial 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 Has an existing Do Not Intubate order Has undergone 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 (eg, obstructive sleep apnea) Has 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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVI-MSC<br>Subjects will receive intravenous infusions of COVI-MSC (two vials or a total of ≈ 30 million cells) on Day 0, Day 2, and Day 4 | Biological: COVI-MSC<br>* COVI-MSC are allogeneic culture-expanded adipose-derived mesenchymal stem cells<br>|
| Placebo Comparator: Placebo<br>Subjects will receive intravenous infusions of placebo (two vials) on Day 0, Day 2, and Day 4 | Drug: Placebo<br>* Excipient solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality rate at Day 28 | All-cause mortality rate at Day 28 | Baseline through Day 28 | 
| Incidence of all adverse events (AEs) (safety) | Safety as assessed by incidence of AEs by type, frequency, severity, and causality using the Common Terminology Criteria for Adverse Events, Version 5 (CTCAEv5) | Baseline through study completion at Day 90 | 
| Incidence of treatment-emergent adverse events (safety) | Safety as assessed by incidence of treatment-emergent AEs (TEAEs) by type, frequency, severity, and causality using CTCAEv5 criteria | Baseline through study completion at Day 90 | 
| Incidence of severe adverse events (safety) | Safety as assessed by incidence of serious AEs (SAEs) by type, frequency, severity, and causality using CTCAEv5 criteria | Baseline through study completion at Day 90 | 
| Incidence of infusion-related adverse events (safety) | Safety as assessed by incidence of Infusion-related AEs (IrAEs) by type, frequency, severity, and causality using CTCAEv5 criteria over 4 hours | Baseline to Hour 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality rate at Day 60 and 90 | All-cause mortality rate at Day 60 and 90 | Baseline through Day 60 and Day 90 | 
| Number of ventilator-free days through Day 28 | Number of ventilator-free days through Day 28 | Baseline through Day 28 | 
| Number of ICU days through Day 28 | Number of ICU days through day 28 | Baseline through Day 28 | 
| Change in clinical status | Change in clinical status as assessed using the WHO Clinical Progression Scale (0-10 scale, where lower score means a better outcome) at Day 28 | Baseline to Day 28 | 
| Change in oxygenation | Change in oxygenation as assessed using PaO2:FiO2 ratio | Baseline to Day 14 Day 28, and Day 60 | 

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