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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19; COVID-19 Pneumonia
• Intervention / Treatment: Biological: Mesenchymal stem cell; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Paulo R Brofman, phD; Phone Number: 1858 +554132711858; Email: paulo.brofman@pucpr.br
• Study Contact Backup: Name: Carmen K Rebelatto, phD; Phone Number: 1858 +554132711858; Email: carmen.rebelatto@pucpr.br

Study Locations

• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80215200
      • Paulo Roberto Slud Brofman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patient: Intravenous infusion of single-dose of Mesenchymal stem cells (MSCs)	Biological: Mesenchymal stem cell; Administration of advanced cell product
Placebo Comparator: Placebo; Intravenous infusion of single-dose of Ringer's lactate, albumin and heparin solution	Other: Placebo; Ringer's lactate, albumin and heparin solution

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Paulo Brofman
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Investigators: Principal Investigator: Paulo R Brofman, phD, Pontifícia Universidade Católica do Paraná

Publications and helpful links

General Publications

• Rebelatto CLK, Senegaglia AC, Franck CL, Daga DR, Shigunov P, Stimamiglio MA, Marsaro DB, Schaidt B, Micosky A, de Azambuja AP, Leitao CA, Petterle RR, Jamur VR, Vaz IM, Mallmann AP, Carraro Junior H, Ditzel E, Brofman PRS, Correa A. Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial. Stem Cell Res Ther. 2022 Mar 21;13(1):122. doi: 10.1186/s13287-022-02796-1.
• Senegaglia AC, Rebelatto CLK, Franck CL, Lima JS, Boldrini-Leite LM, Daga DR, Leitao CA, Shigunov P, de Azambuja AP, Bana E, Marsaro DB, Schaidt B, Micosky A, Jamur VR, Schluga Y, Vaz IM, Ribeiro LL, Correa A, Brofman EPRS. Combined Use of Tocilizumab and Mesenchymal Stromal Cells in the Treatment of Severe Covid-19: Case Report. Cell Transplant. 2021 Jan-Dec;30:9636897211021008. doi: 10.1177/09636897211021008.

Helpful Links

• UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients.
• The combination of tocilizumab and UC-MSC proved to be safe, with no adverse effects, and the results of this case report prove to be a promising alternative in the treatment of patients with severe acute respiratory syndrome due to SARS-CoV-2.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Anticipated): November 26, 2022
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: MSC SARS-CoV-2; U1111-1267-1200 (Other Identifier: UTN - WHO International Clinical Trials Registry Platform); 31935420.7.1001.0020 (Other Identifier: CAAE - Certificado de Apresentação para Apreciação Ética)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No