Efficacy and Safety Evaluation of Mesenchymal Stem Cells for the Treatment of Patients With Respiratory Distress Due to COVID-19

Study Overview
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Brief Summary
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Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

Detailed Description
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This is a prospective, double-blind, randomized, parallel, placebo-controlled pilot clinical trial to assess the efficacy and safety of two infusions of Wharton Jelly mesenchymal stromal cells (WJ-MSC) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. The study will enroll 30 patients who after signing the informed consent will be checked for inclusion and exclusion criteria. Patients will then be randomized (1:1) to one of the 2 treatment arms: Treatment A WJ-MSC/WJ-MSC; Treatment B Placebo/ Placebo. The 2 infusions will be administered endovenously on day 1 (D1) and on D3. Thereafter, patients will be followed-up on days 3, 5, 7, 14, 21, and 28 Once the study is completed, controls will be established at 3 months, 6 months and 12 months as long-term follow-up. The study treatments (A or B) will be added on top of the Standard of Care treatment prescribed by the attending physician. Each dose of MSC-WJ will consist of the intravenous administration of 1E6cells/Kg. Recruitment will be competitive for the centers participating in the study. A Data Safety and Monitoring Board (DSMB) will be established to review safety and efficacy along the trial.

Official Title
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A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19

Conditions
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COVID-19, SARS-CoV 2, Adult Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: XCEL-UMC-BETA
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive PCR fpr SARS-CoV-2 Intensive Care Unit admission for less than 3 days Moderate acute respiratory distress (Berlin criteria definition with 100 mmHg < PaO2/FiO2 ≤ 200 mmHg) Male or female, aged 18 to 70 years old Signed informed consent by the patient or by a legal representative (in this case, can be obtained by phone, although it must be confirmed in writing later, accepted by email) Exclusion Criteria: Expected survival less than 3 days Treatment with immunosuppressive drugs (tocilizumab, sarilumab) with corticosteroids being allowed Neoplastic disease either active or without complete remission Immunosuppressed patients (except treatment with corticosteroids for respiratory distress) Pregnant or lactating women Participation in another clinical trial with an experimental drug in the last 30 days Other pathologies that, in medical judgment, contraindicate participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Wharton-Jelly mesenchymal stromal cells on D1 and D3 | Drug: XCEL-UMC-BETA<br>* Administration on top of the standard administered treatment<br>* Other names: WJ-MSC;|
| Placebo Comparator: Treatment B<br>Placebo on D1 and D3 | Other: Placebo<br>* Administration on top of the standard administered treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality at day 28 | Number of patients who died, by treatment group | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of WJ-MSC | Number of patients with treatment-emergent adverse events, by treatment group | Day 28 | 
| Need for treatment with rescue medication | Number of patients who, after the start of treatment, required rescue medication, by treatment group | Day 28 | 
| Need and duration of mechanical ventilation | Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group | Day 28 | 
| Ventilator free days | Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group. | Day 28 | 
| Evolution of PaO2 / FiO2 ratio | Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group. | Day 28 | 
| Evolution of the SOFA index | Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group. | Day 28 | 
| Evolution of the APACHE II score | Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group. | Day 28 | 
| Duration of hospitalization | Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group. | Day 28 | 
| Evolution of markers of immune response (leucocyte count, neutrophils) | Variation in the count and percentage of leukocytes and neutrophils, by treatment group. | Day 28 | 
| Feasibility of WJ-MSC administration | Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date | Day 28 | 
| Feasibility of WJ-MSC administration | Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment. | Day 28 | 
| Evolution of disease biomarker: polymerase chain reaction (RT-PCR) | Variation in the values of the biomarker, by treatment group. | Day 28 | 
| Evolution of disease biomarker: lactate dehydrogenase (LDH) | Variation in the values of the biomarker, by treatment group. | Day 28 | 
| Evolution of disease biomarker: D-dimer | Variation in the values of the biomarker, by treatment group. | Day 28 | 
| Evolution of disease biomarker: Ferritin | Variation in the values of the biomarker, by treatment group. | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS