Treatment of Severe COVID-19 Pneumonia With Allogeneic Mesenchymal Stem Cells (MSV-COVID)

January 31, 2024 updated by: Red de Terapia Celular

Double Blind, Placebo-controlled, Phase I/II Clinical Trial to Evaluate Safety and Efficacy of Allogeneic Mesenchymal Stem/Stromal Cells MSV-allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (MSV-COVID)

Novel coronavirus disease COVID-19, produced by SARS-CoV-2, 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/stromal 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 double-blind, placebo-controlled, randomized, phase I/II clinical trial to evaluate safety and efficacy of allogeneic MSCs for treatment of severe COVID-19 pneumonia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Novel coronavirus disease COVID-19, produced by SARS-CoV-2, has spread quickly from Wuhan (China) to worldwide. On April 15, 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 SARS-CoV-2 specifically recognize the angiotensin I converting ezyme 2 receptor (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. SARS-CoV-2 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 SARS-CoV-2 enters in blood circulation, it can easily 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/stromal 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 viruses, reducing proinflammatory cytokines and inflammatory cells into the lungs.

These immunomodulatory properties of MSCs support performance of the placebo-controlled, double-blind (neither the participant nor the investigator will know if active drug or placebo is assigned), randomized (assigned by chance), phase I/II clinical trial in which subjects with severe COVID-19 pneumonia will receive either MSCs (1 million cells/kg) or placebo by intravenous injection. The administration of cells will be done only once.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Valladolid, Spain, 47012
        • Hospital Universitario Rio Hortega

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Women or men of ≥ 18 years of age
  2. SARS-CoV-2 infection confirmed by molecular testing.

  3. Admitted to the Intensive Care Unit with pneumonia by COVID-19 infection and intubated in the last 48 hours, that meet at least one of these criteria:

    1. Respiratory distress.
    2. Respiratory rate (RR) ≥ 30 rpm.
    3. Basal oxygen saturation at rest ≤ 93%.
    4. Arterial partial pressure of oxygen (PaO2) / inspiratory fraction of oxygen (FiO2) ≤ 300 mmHg.
  4. Consent of the patient or his/her legal representative for participation in the study.

Exclusion Criteria:

  1. Active tumor disease.
  2. Pregnancy.
  3. Participation in another active clinical trial.
  4. Any circumstance that in the researcher's opinion justifies the patient's non-participation in the trial.
  5. Not consent to participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mesenchymal Stem Cells (MSCs)
Intravenous injection of 1 million MSCs (MSV cells)/Kg suspended in 100 ml of physiological saline solution.
Biological: Mesenchymal Stem Cells (MSCs)
Intravenous injection of 1 million MSCs (MSV cells)/Kg suspended in 100 ml physiological saline solution.
Other Names:
  • MSV (GMP-compliant MSCs manufactured by IBGM in Valladolid)
Placebo Comparator: Placebo
Intravenous injection of 100 ml of physiological saline solution containing no cells
Other: Placebo
Intravenous injection of 100 ml physiological saline solution containing no cells
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients in whom removal of invasive mechanical ventilation (IMV) has been achieved
Time Frame: 0-7 days
Index of therapy success to preserve Intensive Care Unit (ICU) space.
0-7 days
Overall survival
Time Frame: 0-28 days
To measure global success
0-28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete clinical response
Time Frame: 0-Event/Loss to follow-up
Proportion of patients over time that meet the weaning criteria, defined as (i) PaO2/FiO2 ≥ 200 mmHg, (ii) mechanical ventilation with PEEP ≤ 8 (only if BMI<30), (iii) mechanical ventilation with FiO2 ≤ 50% and (iv) no continuous relaxation (cisatracurium) or prone maneuvers in the last 24 hours.
0-Event/Loss to follow-up
Complete radiological response
Time Frame: 0-28 days
Proportion of patients over time that show lung images free from opacities or condensations
0-28 days
Removal of invasive mechanical ventilation (IMV)
Time Frame: 0-28 days
Proportion of patients over time that reach the event (removal of IMV)
0-28 days
Radiological improvement of pulmonary images
Time Frame: 0-5 days
Change in the proportion of lung sections affected by opacities/condensations in chest X-ray images
0-5 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Levels of cytokines and other inflammatory markers in peripheral blood
Time Frame: 0-7 days
Interleukin-6 (IL-6), D dimer, C reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin.
0-7 days
Levels of circulating immune cells
Time Frame: 0-7 days
B cells, NK cells, T cells, CD4+ T cells, CD8+ T cells
0-7 days
Levels of renal and liver function markers
Time Frame: 0-7 days
Urea, creatinine, gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT).
0-7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Red de Terapia Celular

Collaborators

Castilla-León Health Service
Instituto de Salud Carlos III
University of Valladolid
Hospital del Río Hortega
Citospin

Investigators

  • Study Chair: Julia Barbado, MD, PhD, University Hospital Río Hortega, Valladolid, Spain
  • Study Director: Rosa Conde, PhD, University Hospital Río Hortega, Valladolid, Spain
  • Principal Investigator: Margarita González-Vallinas, PhD, University of Valladolid

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2020

Primary Completion (Actual)

October 28, 2021

Study Completion (Actual)

October 28, 2021

Study Registration Dates

First Submitted

April 17, 2020

First Submitted That Met QC Criteria

April 23, 2020

First Posted (Actual)

April 24, 2020

Study Record Updates

Last Update Posted (Actual)

February 2, 2024

Last Update Submitted That Met QC Criteria

January 31, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TerCel_007
  • 2020-001682-36 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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