Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19.

Study Overview
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Brief Summary
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The purpose of this study is evaluate the feasibility, safety and potential efficacy of an advanced cell therapy product for the treatment of patients with SARS-CoV-2 pneumonia.

Detailed Description
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Forty patients with COVID-19 will receive an intravenous infusion of one dose of 1.000.000 umbilical cord mesenchymal cells per kilo of the patient. Twenty patients will receive a placebo (Ringer's lactate solution, albumin and heparin). Conventional treatment will be performed together with the infusion of cells, during the study period. The evaluation times will be at pre-infusion, 6 and 24 hours, days 5 and 28, 3 and 6 months. The patient exams performed: serology, biochemistry, blood count and blood gas analysis, metabolomics/proteomics, antibody evaluation, electrocardiogram, CT-scan and X-ray, cytokines, viral load, cytometry, and clinical evaluation. The patients will be evaluated all the time, during hospitalization period, to assess adverse events.

Official Title
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Multicenter Phase I/IIa Study of Mesenchymal Stromal Cells for the Treatment of Patients With SARS-CoV-2 Pneumonia.

Conditions
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COVID-19 Pneumonia, COVID-19

Intervention / Treatment
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* Biological: Mesenchymal stem cell
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both sexes; aged 18 to 79 years old; hospitalized patients; radiological diagnosis of viral pneumonia; virological diagnosis of SARS-CoV-2 infection; with noninvasive ventilatory support; C-reactive protein and ferritin above the reference value considered normal; assent confirmed to participate in the study. Exclusion Criteria: Contraindications for use of corticosteroids; immunosuppressive, cytotoxic and antiviral treatment, experimental medications and chronic corticosteroid use; morbid obesity (BMI> 35); multiple organ dysfunction syndrome; pre-malignant neoplastic conditions with life expectancy lower than 1 year old; pre-existing chronic illnesses like chronic dialysis kidney disease, chronic liver disease, congestive heart failure Class IV; pulmonary hypertension (WHO Class III/IV); pre-existing or current thromboembolic pathology; transplanted patients; pre-existing severe allergic reaction; history of HIV and tuberculosis; enrollment in another clinical trial; pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Treatment<br>Patient: Intravenous infusion of single-dose of Mesenchymal stem cells (MSCs) | Biological: Mesenchymal stem cell<br>* Administration of advanced cell product<br>|
| Placebo Comparator: Placebo<br>Intravenous infusion of single-dose of Ringer's lactate, albumin and heparin solution | Other: Placebo<br>* Ringer's lactate, albumin and heparin solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of intravenously infused UCT-MSC suspension | The primary expected outcome is the safety and tolerability of using intravenously infused UTC-MSC suspension in patients with pneumonia caused by SARS-CoV-2. This outcome will be evaluated by recording adverse events that must be reported throughout the study period. | After first cell infusion until the end of study. The clinical follow-up of patients will be one year after the transplant. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function test to evaluate the improvement of respiratory function | Evaluation of lung function. | Pre-infusion, on days 5 and 28, 3 and 6 months. | 
| Radiography to evaluate the improvement of respiratory function | Evaluation of pulmonary function using breathing chest radiography. Assessment of peripheral opacities, interstitial and airspace opacities, diffuse airspace opacities, interstitial opacities, lobar consolidation, atelectasis, cavities, pulmonary cysts, and emphysema. | Pre-infusion, on days 5 and 28, 3 and 6 months. | 
| 6-minute walk to evaluate the improvement of respiratory function | Distance covered by the patient in a period of 6 minutes. | Pre-infusion, on days 5 and 28, 3 and 6 months. | 
| Decrease on days of non-invasive mechanical ventilation | Analysis of ventilatory parameters and arterial blood gas analysis. | Six hours after infusion, days 1, 5 and 28, 3 and 6 months. | 
| Biochemical tests to evaluate the improvement of laboratory parameters | D-dimer, C-reactive protein, erythrocyte sedimentation rate, ferritin, creatine, urea, saline, potassium, bilirubin, total protein and fractions, albumin, globulin, oxalacetic transaminase, pyruvic transaminase, lactate dehydrogenase, creatine phosphokinase, troponin I, coagulogram. | Pre-infusion, on days 1, 5 and 28, 3 and 6 months. | 
| Blood count to evaluate the improvement of laboratory parameters | Red blood cells, hemoglobin, hematocrit, total leukocytes, basophil, eosinophil, neutrophil, lymphocytes, monocytes, platelets. | Pre-infusion, on days 1, 5 and 28, 3 and 6 months. | 
| Viral load to evaluate the improvement of laboratory parameters | Expression of the RpRd gene. | Pre-infusion, on days 1, 5 and 28, 3 and 6 months. | 
| Cytokine dosage to evaluate inflammatory parameters | Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL) -2, IL-6, IL-7, IL-8, tumor necrosis factor (TNF) α, monocyte chemoattractant protein-1 (MCP1/CCL2) and macrophage inflammatory protein 1-alpha (MIP1a/CCL3). | Pre-infusion, on days 1, 5 and 28, 3 and 6 months. | 
| Decrease in hospital stay | Evaluation of hospitalization days. | From admission to discharge, or a maximum of 6 months. | 
| Computed tomography score to evaluate the improvement of pulmonary function | Chest computed tomography evaluation will analyze the following characteristics: ground glass opacities, linear opacities, consolidation, interlobular septal thickening, crazy-paving pattern, subpleural lines, bronchial wall thickening, lymph node enlargement and pleural effusion. Lesions will quantify by assigning a score to all abnormal areas involved. Each lobe will assigned a score of 0 (0% involvement), 1 (1-25% involvement), 2 (26-50% involvement), 3 (51-75% involvement) or 4 (76%-100% involvement). The total score will be the sum of all lobes, ranging from 0 to 25. | Pre-infusion, on days 5 and 28, 3 and 6 months. | 
| Reduction in the percentage of intubated patients | Clinical evaluation of patients. | After first cell infusion until six months after the transplant. | 
| Decrease in mortality | Evaluation of the number of patients who died during the study. | After first cell infusion until the end of study. The clinical follow-up of patients will be six months after the transplant. |