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

COVID-19 Pneumonia Clinical Trial

— MSV-COVID  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04361942
• Other study ID #: TerCel_007
• Secondary ID: 2020-001682-36
• Status: Completed
• Phase: Phase 2
• Start date: May 1, 2020
• Est. completion date: October 28, 2021

Study information

• Verified date: January 2024
• Source: Red de Terapia Celular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 28, 2021
• Est. primary completion date: October 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Pneumonia

Intervention

Biological:
• Mesenchymal Stem Cells (MSCs)
Intravenous injection of 1 million MSCs (MSV cells)/Kg suspended in 100 ml physiological saline solution.

Other:
• Placebo
Intravenous injection of 100 ml physiological saline solution containing no cells

Locations

Country	Name	City	State
Spain	Hospital Universitario Rio Hortega	Valladolid

Sponsors (6)

Lead Sponsor	Collaborator
Red de Terapia Celular	Castilla-León Health Service, Citospin, Hospital del Río Hortega, Instituto de Salud Carlos III, University of Valladolid

Country where clinical trial is conducted

Spain, 

References & Publications (4)

Barbado J, Tabera S, Sanchez A, Garcia-Sancho J. Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis. Lupus. 2018 Nov;27(13):2161-2165. doi: 10.1177/0961203318804922. Epub 2018 Oct 5. — View Citation

Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, Shan G, Meng F, Du D, Wang S, Fan J, Wang W, Deng L, Shi H, Li H, Hu Z, Zhang F, Gao J, Liu H, Li X, Zhao Y, Yin K, He X, Gao Z, Wang Y, Yang B, Jin R, Stambler I, Lim LW, Su H, Moskalev A, Cano A, Chakrabarti S, Min KJ, Ellison-Hughes G, Caruso C, Jin K, Zhao RC. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis. 2020 Mar 9;11(2):216-228. doi: 10.14336/AD.2020.0228. eCollection 2020 Apr. — View Citation

Noriega DC, Ardura F, Hernandez-Ramajo R, Martin-Ferrero MA, Sanchez-Lite I, Toribio B, Alberca M, Garcia V, Moraleda JM, Sanchez A, Garcia-Sancho J. Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells: A Randomized Controlled Trial. Transplantation. 2017 Aug;101(8):1945-1951. doi: 10.1097/TP.0000000000001484. — View Citation

Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sanchez A, Garcia-Sancho J. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Transplantation. 2015 Aug;99(8):1681-90. doi: 10.1097/TP.0000000000000678. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Levels of cytokines and other inflammatory markers in peripheral blood	Interleukin-6 (IL-6), D dimer, C reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin.	0-7 days
Other	Levels of circulating immune cells	B cells, NK cells, T cells, CD4+ T cells, CD8+ T cells	0-7 days
Other	Levels of renal and liver function markers	Urea, creatinine, gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT).	0-7 days
Primary	Proportion of patients in whom removal of invasive mechanical ventilation (IMV) has been achieved	Index of therapy success to preserve Intensive Care Unit (ICU) space.	0-7 days
Primary	Overall survival	To measure global success	0-28 days
Secondary	Complete clinical response	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
Secondary	Complete radiological response	Proportion of patients over time that show lung images free from opacities or condensations	0-28 days
Secondary	Radiological improvement of pulmonary images	Change in the proportion of lung sections affected by opacities/condensations in chest X-ray images	0-5 days
Secondary	Removal of invasive mechanical ventilation (IMV)	Proportion of patients over time that reach the event (removal of IMV)	0-28 days