Treatment of Severe COVID-19 Pneumonia With Allogeneic Mesenchymal Stromal Cells (COVID_MSV)

Study Overview
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Brief Summary
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Novel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.

Detailed Description
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Novel coronavirus COVID-19 has spread quickly from Wuhan China to worldwide. On 15 April 2020, the World Health Organization (WHO) has reported 1.914.916 confirmed cases and 123.010 deaths globally, being a severe threat to public health. Some patients develop overwhelming lung inflammation and acute respiratory failure. Several reports demonstrated that COVID-19 specifically recognized the angiotensin I converting ezyme 2 repector (ACE2) and ACE2-positive cells are infected by the virus. ACE2 receptor is widely present on the human cells surface such as alveolar type II cells and capillary endothelium, among others. COVID-19 infects cells and stimulates a terrible cytokine storm in the lung followed by edema, dysfunction of the air exchange and acute respiratory distress which may lead to death. Further, once COVID-19 enters in blood circulation, it can easy spread to some systems and organs, causing significant damage. Under these circumstances, it is reasonable to believe that the inhibition of inflammatory response is the key to treat COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. Some studies have shown that MSCs can significantly reduce acute lung injury in mice caused by H9N2 and H5N1 virus, reducing proinflammatory cytokines and inflammatory cells into the lungs. These immunomodulatory properties of MSCs support performance of the Phase I/II, double-blind (neither the participant nor the investigator will know if active drug or placebo is assigned), placebo-controlled, randomized (assigned by chance), in which subjects with severe COVID-19 pneumonia shall be received either MSCs (1 million cells/kg) or placebo by intravenous injection. The administration of cells will be done only once.

Official Title
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Double Blind, Placebo-controlled, Phase II Trial to Evaluate Safety and Efficacy of Allogenic Mesenchymal Stromal Cells MSV_allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (COVID_MSV)

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Biological: Mesenchymal Stromal Cells
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men of ≥ 18 years of age SARS-CoV-2 infection confirmed by molecular testing. Admitted to the Intensive Care Unit with pneumonia by COVID-19 infection in the last 48 hours, that meet at least one of these criteria: Respiratory distress. Respiratory rate (FR) ≥ 30 rpm. Basal oxygen saturation at rest ≤ 93%. Arterial partial pressure of oxygen (PaO₂) / inspiratory fraction of oxygen (FiO₂) ≤300mmHg Consent of the patient or his legal representative for participation in the study. Exclusion Criteria: Active tumor disease. Pregnancy. Participation in another clinical trial for the same pathology. Any circumstance that in the researcher's opinion justifies the patient's non-participation in the trial. Lack of signed consent for participation.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Intravenous injection of 1 million MSV cells/Kg in 100 ml of saline | Biological: Mesenchymal Stromal Cells<br>* Intravenous injection of 1 million MSV cells/Kg diluted in 100 ml saline<br>* Other names: MSV;|
| Placebo Comparator: Placebo<br>Intravenous injection of 100 ml of saline containing no cells | Other: Placebo<br>* Intravenous injection of 100 ml saline containing no cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have achieved withdrawal of invasive mechanical ventilation | Index of therapy success to preserve Intensive Care Hospitalization space | 0-7 days | 
| Rate of mortality | To measure global success | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have achieved clinical response | Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2 | 0-7days | 
| Proportion of patients who have achieved radiological responses | Evaluation of pneumonia changes | 0-28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Mesenchymal Stromal Cells, MSV