Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection

Study Overview
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Brief Summary
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The overall objective of the study is to evaluate the safety and efficacy of MSC therapy combined with best supportive care in hospitalized patients with COVID-19.

Detailed Description
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This study is a monocentric prospective phase I/II clinical trial, aiming at evaluating the safety and efficacy of 3 intravenous administrations of BM-MSC in 20 patients with severe to critical COVID-19 pneumonia. After signed informed consent, patients will receive 3 infusions of (1.5)-3.0 x106/kg BM-MSC (from the same donor) at 3-4 days interval, in addition to the standard of care for COVID-19 disease. The trial will be open for inclusion for 2 years after initiation. Each patient will be followed for 90 days after inclusion. The total study duration will thus be 2 years and 90 days.

Official Title
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Mesenchymal Stromal Cell Therapy for Severe Covid-19 Infection

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Biological: Mesenchymal stromal cells


Participation Criteria
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Eligibility Criteria
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COVID-19 patients Inclusion criteria Male or female patients aged at least 18 years and up to 70 years Diagnosed with microbiologically or radiologically confirmed COVID-19 pneumonia as defined by: Extensive interstitial pneumonia on CT scan, consistent with viral pneumonia, within 10 days prior to randomization And either positive result of COVID-19 PCR test within 14 days prior to inclusion or positive result of SARS-CoV2 PCR or serology within 14 days after inclusion. Requiring oxygen administration (SpO2 ≤ 93% on room air): Group A: in standard or intensive care unit requiring supplemental oxygen Group B: in intensive care unit under mechanical ventilation administered through a tracheal tube, either: for less than or equal to 7 days for 7 to 14 days, with persisting high inflammation (ferritin > 2,000 µg/L; ferritin > 1,000 µg/L and rising; lymphocytes < 800 with CRP > 70 mg/L and rising or ferritin > 700 µg/L and rising or LDH > 300 UI/L or D-Dimers > 1000 ng/ml), not explained by superinfection. Rising = compared to previous 24H. Written consent of the patient, or - if impossible (clinical condition precluding capacity to consent) - of his/her legal representative, or - if impossible - of an impartial witness such as a physician from a non-participating department or member of the Ethics Committee. Any consent obtained this way shall be documented and confirmed by way of normal consent procedures at the earliest opportunity when the patient has recovered Exclusion criteria Ongoing pregnancy. Women of childbearing potential (WOCBP, defined as a premenopausal female capable of becoming pregnant) should use an appropriate method of contraception (oral, injectable, or mechanical contraception; women whose partners have been vasectomized or have received or are utilizing mechanical contraceptive devices). Extracorporeal membrane oxygenation Limitations to intensity of care Life expectancy < 24 hours Known allergy to IMP component Active secondary infection Any malignancy (except non-melanoma skin carcinoma) within 2 years before inclusion Pre-existing thrombo-embolic pathology Signs of an active drug or alcohol dependence, serious current illness, mental illness or any factors which, in the opinion of the Investigator, may interfere with subject's ability to understand and comply with study requirements Patients with any serious medical condition or abnormality of clinical laboratory tests that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study. Participation in another clinical trial(use of anti-viral/supportive drugs for COVID-19 infection on a compassionate use basis is not an exclusion criterion). MSC donors Inclusion criteria Unrelated to the patient Male or female Age > 18 yrs No HLA matching required Fulfills generally accepted criteria for allogeneic HSC donation Informed consent given by donor Exclusion criteria Any condition not fulfilling inclusion criteria Known allergy to lidocaine Any risk factor for transmissible infectious diseases, in particular HIV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Interventional Model Description: This study is a monocentric prospective phase I/II clinical trial, aiming at evaluating the safety and efficacy of 3 intravenous administrations of BM-MSC in 20 patients with severe to critical COVID-19 pneumonia.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC therapy for severe COVID-19 infection<br>After signed informed consent, patients will receive 3 infusions of (1.5)-3.0 x106/kg BM-MSC (from the same donor) at 3-4 days interval, in addition to the standard of care for COVID-19 disease. | Biological: Mesenchymal stromal cells<br>* Bone marrow collection and MSC expansion cultures will be carried out at the Laboratory of Cell and Gene Therapy (LTCG) at the University of Liège as described in IMPD and its SOPs.<br>* Other names: MSC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia | To assess the infusional toxicity | Day 28 | 
| To evaluate the safety of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia | To assess the number of Adverse events of special interest : Incidence of infections (bacterial, viral, fungal, parasitic) and thrombo-embolic events. | Day 28 | 
| To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia | Group A (patients not under mechanical ventilation): to determine the pourcentage of patients requiring mechanical ventilation | Day 28 | 
| To evaluate the efficacy of intravenous infusion of MSC in patients with severe to critical COVID-19 pneumonia | Group B (patients under mechanical ventilation): to determine the vital status (dead/alive) | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the clinical status (on a 7-point WHO ordinal scale) | Day 28 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the duration of oxygen therapy and/or mechanical ventilation | Day 28 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the length of stay at the intensive care unit and of hospitalization | Day 90 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the number of organ failures | Day 28 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the intensity of the inflammatory response | Day 28 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the evolution of coagulation parameter | Day 28 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the presence of Biomarker of lung lesion, repair and scarring | Day 28 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the v iral load over the 28 days after inclusion and seroconversion to COVID-19 over the 90 days after inclusion | Day 90 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the pulmonary function | Day 90 | 
| To evaluate the effect of MSC administration associated with the standard of care (SOC including anti-viral therapy) | To assess the number of adverse reactions (ARs), ARs grade > 3, serious adverse events (SAEs), serious ARs (SARs), suspected expected and unexpected SARs (SESARs and SUSARs). | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesenchymal stromal cells