SARS-CoV-2 pneumonia MedDRA version: 22.1 Level: LLT Classification code 10061229 Term: Lung infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: cellule adipose perivascolari stromali mesenchimali
Product Code: [RR002]
Pharmaceutical Form: Suspension for injection
Current Sponsor code: RR002
Concentration unit: Other
Concentratio
Sponsors
AZIENDA OSPEDALIERO-UNIVERSITARIA DI MODENA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult patients suffering from SARS-CoV-2 induced severe pneumonia admitted to semi-intensive or intensive COVID Units because of the need of ventilation support. • Sign of the informed consent, • Patients of either sex, aged 18-80 years (inclusive), • Patient with a confirmed virological diagnosis of SARS-CoV2 infection by means of real-time Polymerase Chain Reaction, • Hospitalization due to clinical and radiological diagnosis of pneumonia, • PaO2/FiO2 value between 150-300 with impending necessity of noninvasive positive pressure respiratory support (nCPAP) or ventilator support through nasal pressure support ventilation (nPSV), • Systolic artery pressure >90 mmHg without amine support, • Modified Early Warning Score (MEWS) score =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Deny to informed consent, • Known history of alcohol or drug abuse in the 12 months prior to inclusion, • Presence of significant comorbidities, such as uncontrolled hypertension, invalidating psychiatric or neurological disorders, organ failure (renal impairment defined by creatinine clearance below 50 ml/min or by serum creatinine =2.0 mg/dl; hepatic impairment defined by total bilirubin =2.0 mg/dl and AST + ALT = 2.5 x upper normal value; cardiac failure with an output fraction =40%), or any other clinically significant condition, as determined by the Principal Investigator, • Presence of chronic advanced cardio-pulmonary diseases, such as ILDs (obstructive pneumonia, severe pulmonary interstitial fibrosis, alveolar proteinosis, allergic alveolitis), • Patient has a clinically relevant abnormality on electrocardiogram, as determined by the Principal Investigator, • History of previous embolism, • Known active malignancy, • Patient with a history of severe allergic reactions (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) requiring medical intervention, • Patient with a positive test for human immunodeficiency virus or active hepatitis B or C disease or tuberculosis or further viral infections (influenza virus, adenovirus and other respiratory viruses), • Patient is known to be pregnant, has a positive pregnancy test or is nursing, • Patient has had major surgery, either open or laparoscopic, within the 3 months prior to screening, • Previous haematopoietic stem cell or organ transplantation, • Patient under immunosuppressive agents, • Patients currently receiving, or having received within 2 months prior to enrolment into this clinical study, any other investigational drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of the feasibility and safety of the use of allogeneic Mesenchymal stromal cells (MSC) to treat SARS-CoV-2 related severe pneumonia through the capability to treat all enrolled patients and monitoring the rate of adverse events;Secondary Objective: Evaluation of the efficacy of MSC in terms of: mortality rate trend of the daily PaO2/FiO2 ratio evaluation of the days to intubation date of independence from non-invasive mechanical ventilation date of independence from oxygen therapy hospitalization lenght radiological pattern response Evaluation of: neutrophil, lymphocyte and platelet counts, platelet mean volume, C-reactive protein, ferritin, procalcitonin, LDH, fibrinogen, and D-dimer. Comparative immunological study of the cytokine pattern and the immunophenotyphic cell profile of bronchoalveolar lavage fluid and peripheral blood samples will be carried out in order to establish the pathogenic mechanisms of COVID-19 tissue injury and the mechanism of action of MSC in this specific clinical setting. Establish which IMP used, as stratified according to the tissue origin, is associated with the best result in terms of safety and efficacy.;Primary end point(s): The feasibility will be assessed through the evaluation of the production capacity of each Cell Factory participating in the study in terms of an adequate amount of cellular product lots sufficient to treat 100% of the patients recruited. In addition, the process of transfer of the cellular product to the Clinical Unit will be validated, so that all the quality, safety and therapeutic properties will be guaranteed, with particular reference to its viability. Finally, a protocol for the bedside preparation of the final suspension for administration will be implemented according to the Good Clinical Practice. The safety will be assessed by recording all adverse events as coded by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, based on their duration, intens | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The efficacy will be assessed through the evaluation of a) mortality rate (%) at 2 and 4 weeks from the end of the treatmentfollow-up, b) percentage of change of the daily PaO2/FiO2 ratio in comparison with the basal value, c) percentage of patients under invasive mechanical ventilation, d) days under non-invasive mechanical ventilation, e) days under oxygen therapy, f) radiological response, g) days of hospitalization, h) percentage change of the radiologic score with respect to the basal value; Change of the following laboratory values after 2 and 4 weeks from the end of the MSC treatment of follow-up in comparison to the basal values and expressed as percentages: neutrophil, lymphocyte and platelet counts, platelet mean volume, C-reactive protein, ferritin, procalcitonin, LDH, fibrinogen, and D-dimer.; Modification of the cytokine pattern and of the immunophenotyphic cell profile on both BALF and peripheral blood samples as assessed by means of ELISA, flow cytometry and single cell RNAseq before and after 1 and 2 weeks from the end of MSC treatment follow-up will be carried outevaluated.; We have planned to treat a group of 10 cases with umbilical cord MSCs, a group of 10 cases with umbilical cord blood MSCs, a group of 10 cases with bone marrow MSCs, and a group of 10 cases with adipose tissue MSCs. The percentages of total adverse events, SUSARs, and SARs related to the MSC treatment, together with the efficacy parameters will be compared among the groups.;Timepoint(s) of evaluation of this end point: Endpoints will be assessed at 4 hours, 48 ¿¿hours, 7, 14, and 28 days from the end of treatment or enrollment, as appropriate; End points will be assessed after 2 and 4 weeks from the end of the MSC treatment; End points will be assessed after 1 and 2 weeks from the end of the MSC treatment; End points will be assessed at 4 hours, 48 ¿¿hours, 7, 14, 28 and 180 days from the end of treatment or enrollment | — |
Countries
Italy
Contacts
Public ContactProf. Massimo Dominici
Azienda Ospedaliero-Universitaria Policlinico di Modena
Outcome results
None listed