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

COVID-19 Clinical Trial

— COVIDMES  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04390139
• Other study ID #: BST-COVID-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 13, 2020
• Est. completion date: December 20, 2022

Study information

• Verified date: January 2023
• Source: Banc de Sang i Teixits
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 20, 2022
• Est. primary completion date: December 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Adult Respiratory Distress Syndrome
• COVID-19
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• SARS-CoV 2
• Syndrome

Intervention

Drug:
• XCEL-UMC-BETA
Administration on top of the standard administered treatment

Other:
• Placebo
Administration on top of the standard administered treatment

Locations

Country	Name	City	State
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Mútua de Terrassa	Terrassa	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Banc de Sang i Teixits

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Analysis of subpopulations of lymphocytes and immunoglobulins	Blood sample analysis	Day 28
Other	Evaluation of the in vitro response of the receptor lymphocytes	In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)	Day 28
Other	Study of reactivity against SARS-CoV-2 peptides	Reactivity will be assessed using ELISPOT	Day 28
Other	Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides	Blood sample analysis	Day 28
Other	Genetic variability of patient's genotype in response to treatment	Blood sample analysis for the patient's genomic sequencing	Day 28
Other	Genetic variability of the SARS-CoV-2 genotype in response to treatment	Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample	Day 28
Primary	All-cause mortality at day 28	Number of patients who died, by treatment group	Day 28
Secondary	Safety of WJ-MSC	Number of patients with treatment-emergent adverse events, by treatment group	Day 28
Secondary	Need for treatment with rescue medication	Number of patients who, after the start of treatment, required rescue medication, by treatment group	Day 28
Secondary	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
Secondary	Ventilator free days	Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.	Day 28
Secondary	Evolution of PaO2 / FiO2 ratio	Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.	Day 28
Secondary	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
Secondary	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
Secondary	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
Secondary	Evolution of markers of immune response (leucocyte count, neutrophils)	Variation in the count and percentage of leukocytes and neutrophils, by treatment group.	Day 28
Secondary	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
Secondary	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
Secondary	Evolution of disease biomarker: polymerase chain reaction (RT-PCR)	Variation in the values of the biomarker, by treatment group.	Day 28
Secondary	Evolution of disease biomarker: lactate dehydrogenase (LDH)	Variation in the values of the biomarker, by treatment group.	Day 28
Secondary	Evolution of disease biomarker: D-dimer	Variation in the values of the biomarker, by treatment group.	Day 28
Secondary	Evolution of disease biomarker: Ferritin	Variation in the values of the biomarker, by treatment group.	Day 28

External Links

•   Blood and Tissue Bank of Catalonia
•   Hospital Clínic de Barcelona
•   Hospital de Bellvitge
•   Hospital del Mar
•   Hospital Vall d'Hebron
•   Mútua de Terrassa