Treatment of Severe COVID-19 Pneumonia With Allogeneic Mesenchymal Stromal Cells (COVID_MSV) (COVID_MSV)

• ClinicalTrials.gov Identifier: NCT04361942
• Recruitment Status: Recruiting
• First Posted: April 24, 2020
• Last Update Posted: March 10, 2021
• Sponsor: Red de Terapia Celular
• Collaborators: Citospin; University of Valladolid; Castilla-León Health Service; Hospital del Río Hortega; Instituto de Salud Carlos III
• Information provided by (Responsible Party): Red de Terapia Celular

Study Description

Brief Summary:

Novel coronavirus COVID-19 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 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 phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.

Condition or disease	Intervention/treatment	Phase
COVID-19 Pneumonia	Biological: Mesenchymal Stromal Cells; Other: Placebo	Phase 2

Detailed Description:

Novel coronavirus COVID-19 has spread quickly from Wuhan China to worldwide. On 15 April 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 COVID-19 specifically recognized the angiotensin I converting ezyme 2 repector (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. COVID-19 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 COVID-19 enters in blood circulation, it can easy 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 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 virus, reducing proinflammatory cytokines and inflammatory cells into the lungs.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Both experimental and Placebo will receive a similar endovenous injection with either cells or placebo. Blind to participant, investigator ans care providers
• Primary Purpose: Treatment
• Official Title: Double Blind, Placebo-controlled, Phase II Trial to Evaluate Safety and Efficacy of Allogenic Mesenchymal Stromal Cells MSV_allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (COVID_MSV)
• Actual Study Start Date: May 1, 2020
• Estimated Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Experimental; Intravenous injection of 1 million MSV cells/Kg in 100 ml of saline	Biological: Mesenchymal Stromal Cells; Intravenous injection of 1 million MSV cells/Kg diluted in 100 ml saline; Other Name: MSV
Placebo Comparator: Placebo; Intravenous injection of 100 ml of saline containing no cells	Other: Placebo; Intravenous injection of 100 ml saline containing no cells

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients who have achieved withdrawal of invasive mechanical ventilation [ Time Frame: 0-7 days ]
   Index of therapy success to preserve Intensive Care Hospitalization space
2. Rate of mortality [ Time Frame: 28 days ]
   To measure global success

Secondary Outcome Measures :

1. Proportion of patients who have achieved clinical response [ Time Frame: 0-7days ]
   Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2
2. Proportion of patients who have achieved radiological responses [ Time Frame: 0-28 days ]
   Evaluation of pneumonia changes

Other Outcome Measures:

1. Blood white cell counts and their subpopulations. [ Time Frame: 0-180 days ]
   Haemogram and cell subpopulations
2. Cellular markers of inflammation [ Time Frame: 0-180 days ]
   Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs
3. Cytokines and chemokines in peripheral blood [ Time Frame: 0-180 days ]
   IL-10, IL-6, IP-10, TNF-alpha

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 in the last 48 hours, that meet at least one of these criteria:

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

Exclusion Criteria:

1. Active tumor disease.
2. Pregnancy.
3. Participation in another clinical trial for the same pathology.
4. Any circumstance that in the researcher's opinion justifies the patient's non-participation in the trial.
5. Lack of signed consent for participation.

Contacts and Locations

Contacts

Contact: Julia Barbado, MD,PhD; +34 616 73 40 03; jbarbadoa@saludcastillayleon.es

Contact: Rosa Conde, MD, PhD; +34 608 21 28 65; rconvi@saludcastillayleon.es

Locations

Spain

Hospital Universitario Rio Hortega; Recruiting

Valladolid, Spain, 47012

Contact: Julia Barbado, MD, PhD +34 983 420400 jbarbadoa@saludcastillayleon.es

Contact: Rosa Conde, MD, PhD +34 983 420400 'Rosa Conde Vicente' <rconvi@saludcastillayleon.es>

Sponsors and Collaborators

Red de Terapia Celular

Citospin

University of Valladolid

Castilla-León Health Service

Hospital del Río Hortega

Instituto de Salud Carlos III

Investigators

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

More Information

Publications of Results:

Vega A, Martín-Ferrero MA, Del Canto F, Alberca M, García V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sánchez A, García-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.

Noriega DC, Ardura F, Hernández-Ramajo R, Martín-Ferrero MÁ, Sánchez-Lite I, Toribio B, Alberca M, García V, Moraleda JM, Sánchez A, García-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.

Barbado J, Tabera S, Sánchez A, García-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.

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.

• Responsible Party: Red de Terapia Celular
• ClinicalTrials.gov Identifier: NCT04361942
• Other Study ID Numbers: TerCel_007; 2020-001682-36 ( EudraCT Number )
• First Posted: April 24, 2020
• Last Update Posted: March 10, 2021
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Red de Terapia Celular:

COVID-19; Mesenchymal Stromal Cells; MSV

Additional relevant MeSH terms:

Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections