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

• ClinicalTrials.gov Identifier: NCT04390139
• Recruitment Status: Active, not recruiting
• First Posted: May 15, 2020
• Last Update Posted: April 26, 2022
• Sponsor: Banc de Sang i Teixits
• Information provided by (Responsible Party): Banc de Sang i Teixits

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19; SARS-CoV 2; Adult Respiratory Distress Syndrome	Drug: XCEL-UMC-BETA; Other: Placebo	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 13, 2020
• Estimated Primary Completion Date: May 2022
• Estimated Study Completion Date: October 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment A; Wharton-Jelly mesenchymal stromal cells on D1 and D3	Drug: XCEL-UMC-BETA; Administration on top of the standard administered treatment; Other Name: WJ-MSC
Placebo Comparator: Treatment B; Placebo on D1 and D3	Other: Placebo; Administration on top of the standard administered treatment

Outcome Measures

Primary Outcome Measures :

1. All-cause mortality at day 28 [ Time Frame: Day 28 ]
   Number of patients who died, by treatment group

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Analysis of subpopulations of lymphocytes and immunoglobulins [ Time Frame: Day 28 ]
   Blood sample analysis
2. Evaluation of the in vitro response of the receptor lymphocytes [ Time Frame: Day 28 ]
   In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)
3. Study of reactivity against SARS-CoV-2 peptides [ Time Frame: Day 28 ]
   Reactivity will be assessed using ELISPOT
4. Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides [ Time Frame: Day 28 ]
   Blood sample analysis
5. Genetic variability of patient's genotype in response to treatment [ Time Frame: Day 28 ]
   Blood sample analysis for the patient's genomic sequencing
6. Genetic variability of the SARS-CoV-2 genotype in response to treatment [ Time Frame: Day 28 ]
   Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Positive PCR fpr SARS-CoV-2
2. Intensive Care Unit admission for less than 3 days
3. Moderate acute respiratory distress (Berlin criteria definition with 100 mmHg < PaO2/FiO2 ≤ 200 mmHg)
4. Male or female, aged 18 to 70 years old
5. 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:

1. Expected survival less than 3 days
2. Treatment with immunosuppressive drugs (tocilizumab, sarilumab) with corticosteroids being allowed
3. Neoplastic disease either active or without complete remission
4. Immunosuppressed patients (except treatment with corticosteroids for respiratory distress)
5. Pregnant or lactating women
6. Participation in another clinical trial with an experimental drug in the last 30 days
7. Other pathologies that, in medical judgment, contraindicate participation in the study

Contacts and Locations

Locations

Spain

Hospital de Bellvitge

Hospitalet de Llobregat, Barcelona, Spain, 08907

Mútua de Terrassa

Terrassa, Barcelona, Spain, 08221

Hospital del Mar

Barcelona, Spain, 08003

Hospital Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clínic de Barcelona

Barcelona, Spain, 08036

Sponsors and Collaborators

Banc de Sang i Teixits

Investigators

• Study Chair: Antoni Torres, MD, PhD; Hospital Clinic of Barcelona

More Information

Additional Information:

Blood and Tissue Bank of Catalonia 

Hospital Cl&#237;nic de Barcelona 

Hospital Vall d'Hebron 

Hospital del Mar 

M&#250;tua de Terrassa 

Hospital de Bellvitge 

• Responsible Party: Banc de Sang i Teixits
• ClinicalTrials.gov Identifier: NCT04390139
• Other Study ID Numbers: BST-COVID-01
• First Posted: May 15, 2020
• Last Update Posted: April 26, 2022
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Banc de Sang i Teixits:

ARDS

Additional relevant MeSH terms:

COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome; Disease; Pathologic Processes; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury