Clinical Trial of Allogeneic Mesenchymal Cells From Umbilical Cord Tissue in Patients With COVID-19 (MESCEL-COVID19)

Phase II Clinical Trial to Explore the Efficacy of Allogeneic Mesenchymal Cells From Umbilical Cord Tissue in Patients With Severe Pulmonary Involvement by COVID-19

The disease caused by the SARS-CoV-2 virus is a viral disease that infects the lungs, producing flu-like symptoms. Elderly infected patients and/or those with co-morbidities may suffer from acute respiratory distress syndrome due to pneumonia (COVID-19 disease). Given the high transmission, this virus has spread in recent months from Wuhan (China) to the whole world, becoming a global emergency pandemic. The lack of curative treatment for this disease justifies the need to carry out clinical trials that provide quality evidence on treatment options. Given the pathophysiology of the disease, which involves an uncontrolled inflammatory response of alveolar cells, a treatment that attenuates the cytokine cascade could be key in rescuing the patient's lung tissue. Mesenchymal cells, due to their immunoregulatory potential and regenerative capacity, can be an effective treatment for patients infected with the SARS-CoV-2 virus.

In the present study we propose a therapy with undifferentiated allogeneic mesenchymal cells derived from umbilical cord tissue, a treatment whose safety has already been described in other clinical trials and that shows promising results in pilot studies carried out in China.

Study Overview

• Status: Withdrawn
• Conditions: COVID
• Intervention / Treatment: Biological: Mesenchymal cells; Drug: Standard of care

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barakaldo, Spain, 48903
    • Hospital Universitario de Cruces
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Niño Jesús
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28046
    • Complejo Universitario La Paz
  • Madrid
    • Getafe, Madrid, Spain, 28320
      • Hospital Universitario de Getafe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged between 40 and 80 years
2. Body weight between 50 kg and 100 kg
3. PCR diagnosis of SARS-CoV-2 virus infection

4. Clinical diagnosis of severe lung involvement associated with SARSCoV- 2 virus infection according to the criteria of the National Health Commission of China, that is, patients who meet at least one of the following criteria:

   1. Respiratory distress with ≥ 30 breaths per minute; or
   2. Oxygen saturation ≤ 93% at baseline; or
   3. Partial arterial oxygen pressure (PaO2) / Fraction of inspiration of O2 (FiO2) ≤300mmHg. (PaO2 / FiO2 is accepted based on SatO2). Patients who do not require respiratory support, or who require noninvasive respiratory support (conventional, high-flow oxygen therapy, or non-invasive mechanical ventilation) are considered eligible.
5. Patients who are already receiving the standard medical treatment available for severe lung involvement associated with SARS-CoV-2 virus infection or any of the standard treatments are contraindicated in the patient and cannot be used and it is necessary to consider other alternatives.
6. Women who are surgically sterile or postmenopausal or women of childbearing potential with negative urine or serum pregnancy test or men willing to use condoms for the entire duration of the study or for three months after the last dose of the investigational drug, whichever is later, or have a partner who is using a contraceptive method with high efficacy, such as described above.
7. Signed informed consent.

Exclusion Criteria:

1. Clinical diagnosis of critically serious lung involvement associated with SARS-CoV-2 virus infection according to the criteria of the National Health Commission of China, that is, patients who meet any of the following criteria:

   1. Respiratory failure requiring invasive mechanical ventilation; or
   2. Shock; or
   3. Combination with failure of another organ; need for ICU admission for monitoring / treatment.
2. Patients who are expected to develop rapidly fatal disease within 72 hours of enrollment.
3. Inability to maintain a mean arterial pressure > 50 mmHg before selection despite the presence of vasopressors and intravenous fluids.
4. Patients requiring treatment with vasopressors (dopamine > 5 mg / kg / min or any dose of epinephrine, norepinephrine, phenylephrine, or vasopressin) for at least 2 hours to maintain systolic blood pressure (SBP) > 90 mmHg (or mean blood pressure [MBP] > 70 mmHg) after adequate fluid administration.
5. Patients who are not expected to live more than 3 months due to other medical illnesses, such as neoplasia or other terminal illnesses.
6. Patients with primary or metastatic lung cancer or with chemotherapy scheduled for the next 90 days.
7. Patients with a known primary immunodeficiency disorder or with acquired immunodeficiency syndrome (HIV infection) with a CD4 count <200 cells / mm3 or who do not have an undetectable viral load (<200 copies).
8. Patients receiving immunosuppressive therapy (including chronic treatment with any alpha antitumor necrosis factor [TNFa]) or corticosteroid therapy.
9. Granulocytopenia, not due to sepsis, evidenced by an absolute neutrophil count <500 per μL.
10. Hematologic or lympho-reticular malignancies, unless in remission.
11. Patients who have received a stem cell, organ, or bone marrow transplant in the last 6 months.
12. Patients in current treatment with a biological product (eg, antibodies, cell therapy) or with plasmapheresis in the last 8 weeks.
13. Patients who are currently receiving or have received another investigational drug in the 90 days prior to study initiation (or 5 halflives of the investigational compound, whichever is longer).
14. Known allergies or hypersensitivity to antibiotics and/or any component of the investigational product.
15. Patients with known severe liver function impairment.
16. Patients with known severe kidney function impairment.
17. Patients admitted in the previous 15 days for causes other than SARS-CoV-2 virus infection.
18. Diseases other than SARS-CoV-2 virus infection leading to New York Heart Association class IV status.
19. Terminal neuromuscular disorders that alter the gradual withdrawal of the ventilator (eg, amyotrophic lateral sclerosis).
20. Patients with complete tetraplegia (traumatic or otherwise).
21. Dementia-Alzheimer and another situation in which is considered patient can not understand what is explaining, can not read or does not understand the language.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal cells; Undifferentiated allogeneic mesenchymal cells derived from umbilical cord tissue	Biological: Mesenchymal cells; 1 infusion of undifferentiated allogeneic mesenchymal cells derived from umbilical cord tissue
Active Comparator: Standard of care	Drug: Standard of care; Best treatment option for COVID-19 according to investigator criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality due to lung involvement due to SARS-CoV-2 virus infection at 28 days of treatment	Percentage of patients death due to lung involvement due to SARS-CoV-2 virus infection at 28 days of treatment	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality due to lung involvement due to SARS-CoV-2 virus infection at 14 days of treatment	Percentage of patients death due to lung involvement due to SARS-CoV-2 virus infection at 14 days of treatment	14 days
Mortality from any cause at 28 days	Percentage of patients death due to any cause at 28 days of treatment	28 days
Days without mechanical respirator and without vasopressor treatment for 28 days	Number of days without mechanical respirator and without vasopressor treatment for 28 days	28 days
Patients alive without mechanical ventilation and without vasopressors on day 28	Percentage of patients alive without mechanical ventilation and without vasopressors on day 28	28 days
Patients alive and without mechanical ventilation on day 14	Percentage of patients alive and without mechanical ventilation on day 14	14 days
Patients alive and without mechanical ventilation on day 28	Percentage of patients alive and without mechanical ventilation on day 28	28 days
Patients alive and without vasopressors on day 28	Percentage of patients alive and without vasopressors on day 28	28 days
Days without vasopressors for 28 days	Number of days without vasopressors for 28 days	28 days
Patients cured at 15 days	Percentage of patients cured at 15 days	15 days
Incidence of Treatment-Emergent Adverse Events	Percentage of patients with each adverse event	1 year

Collaborators and Investigators

• Sponsor: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• Collaborators: Apices Soluciones S.L.
• Investigators: Study Chair: Luis Madero, MD, Hospital Infantil Universitario Niño Jesús, Oncohematology Department

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2020
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; mesenchymal cells from umbilical cord
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: MESCEL-COVID19; 2020-001450-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No