Patients with severe COVID-19 infection MedDRA version: 23.1 Level: LLT Classification code 10084401 Term: COVID-19 respiratory infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: Mesenchymal Stromal Cells
Product Code: MSC
Pharmaceutical Form: Suspension for injection
Sponsors
CHU de Liège
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. COVID-19 patients: • 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 OR for 7 to 14 days, with persisting high inflammation (ferritin > 2,000 µg/L; ferritin > 1,000 µg/L and rising; lymphocytes 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. 2. MSC donors: • 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. COVID-19 patients: • 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). 2. MSC donors: • Any condition not fulfilling inclusion criteria • Known allergy to lidocaine • Any risk factor for transmissible infectious diseases, in particular HIV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: To evaluate the effects of MSC administration associated with the standard of care (SOC including anti-viral therapy) on: 1. Clinical status (on a 7-point WHO ordinal scale) 2. The need for mechanical ventilation and the duration of oxygen therapy and mechanical ventilation 3. The length of stay at the intensive care unit and of hospitalization 4. The number of organ failures 5. The intensity of the inflammatory response 6. Coagulation parameters 7. Biomarkers of lung lesion, repair and scarring 8. Viral load and sero-conversion 9. Pulmonary function (pulmonary function tests and thoracic CT-scan) 10. The number of Adverse reactions (ARs), ARs grade > 3, serious adverse events (SAEs), serious ARs (SARs), suspected expected and unexpected SARs (SESARs/SUSARs).;Primary end point(s): Safety co-primary endpoint: To evaluate the safety of intravenous infusions of BM-MSC in patients with severe to critical COVID-19 pneumonia: • Infusional toxicity (change in body temperature, heart rate, mean arterial blood pressure and peripheral capillary oxygen saturation, and clinical signs of allergy such as skin reaction or anaphylactic shock); • -Adverse events of special interest: Incidence of infections (bacterial, viral, fungal, parasitic) and thrombo-embolic events within the first 28 days after inclusion Efficacy co-primary endpoint: - Group A (patients not under mechanical ventilation): % patients requiring mechanical ventilation by day 28 - Group B (patients under mechanical ventilation): Vital status (dead/alive) at day 28 ;Timepoint(s) of evaluation of this end point: Safety co-primary endpoint: within the first 28 days after inclusion Efficacy co-primary endpoint: - Group A : by day 28 - Group B: at day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the effects of MSC administration associated with the standard of care (SOC including anti-viral therapy) on: 1. Clinical status (on a 7-point WHO ordinal scale) over the 28 days after inclusion 2. The need for mechanical ventilation and the duration of oxygen therapy and mechanical ventilation over the 28 days after inclusion 3. The length of stay at the intensive care unit and of hospitalization 4. The number of organ failures over the 28 days after inclusion 5. The intensity of the inflammatory response during the 28 days following inclusion 6. Coagulation parameters within the first 28 days following inclusion 7. Biomarkers of lung lesion, repair and scarring within the first 28 days following inclusion 8. Viral load over the 28 days after inclusion and sero-conversion to COVID-19 over the 90 days after inclusion 9. Pulmonary function (pulmonary function tests and thoracic CT-scan) at day 90 after inclusion. 10. The number of Adverse reactions (ARs), ARs grade > 3, serious adverse events (SAEs), serious ARs (SARs), suspected expected and unexpected SARs (SESARs/SUSARs).;Timepoint(s) of evaluation of this end point: To evaluate the effects of MSC administration associated with the standard of care (SOC including anti-viral therapy) on: 1. over the 28 days after inclusion 2. over the 28 days after inclusion 3. over the 90 days after inclusion 4. over the 28 days after inclusion 5. during the 28 days following inclusion 6. within the first 28 days following inclusion 7. within the first 28 days following inclusion 8. Viral load over the 28 days after inclusion and sero-conversion to COVID-19 over the 90 days after inclusion 9. at day 90 after inclusion. 10. during all the study | — |
Countries
Belgium
Contacts
Public ContactClinical Trials Information
CHU de Liège
Outcome results
None listed