Clinical trial NCT04361942: Treatment of Severe COVID-19 Pneumonia With Allogeneic Mesenchymal Stem Cells
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19 Pneumonia
Keywords: COVID-19
Mesenchymal Stromal Cells
Mesenchymal Stem Cells
MSV
Lead sponsor: Red de Terapia Celular
Sponsor class: INDUSTRY
Collaborators: name: Citospin
name: University of Valladolid
name: Castilla-León Health Service
name: Hospital del Rio Hortega
name: Instituto de Salud Carlos III
First posted: 2020-04-24
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients in whom removal of invasive mechanical ventilation (IMV) has been achieved
timeFrame: 0-7 days
measure: Overall survival
timeFrame: 0-28 days
Secondary outcomes:
measure: Complete clinical response
timeFrame: 0-Event/Loss to follow-up
measure: Complete radiological response
timeFrame: 0-28 days
measure: Radiological improvement of pulmonary images
timeFrame: 0-5 days
measure: Removal of invasive mechanical ventilation (IMV)
timeFrame: 0-28 days
Other outcomes:
measure: Levels of cytokines and other inflammatory markers in peripheral blood
timeFrame: 0-7 days
measure: Levels of circulating immune cells
timeFrame: 0-7 days
measure: Levels of renal and liver function markers
timeFrame: 0-7 days
Locations:
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
Study officials:
affiliation: University Hospital Río Hortega, Valladolid, Spain
name: Julia Barbado, MD, PhD
role: STUDY_CHAIR
affiliation: University Hospital Río Hortega, Valladolid, Spain
name: Rosa Conde, PhD
role: STUDY_DIRECTOR
affiliation: University of Valladolid
name: Margarita González-Vallinas, PhD
role: PRINCIPAL_INVESTIGATOR
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