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    Summary
    EudraCT Number:2020-001577-70
    Sponsor's Protocol Code Number:RESCAT
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-10-21
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2020-001577-70
    A.3Full title of the trial
    Allogeneic Mesenchymal Stromal Cell (MSC) Therapy for SARS-CoV-2 Pneumonia: A Prospective Randomized Multicentre Phase I/IIa Open Label Study
    Studio prospettico randomizzato multicentrico di fase I/IIa sull’impiego di cellule stromali mesenchimali allogeniche nel trattamento di pazienti affetti da polmonite da SARS-CoV-2
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical study on mesenchymal Cell Therapy for SARS-CoV-2 Pneumonia
    Studio clinico sull’impiego di cellule mesenchimali nel trattamento di pazienti affetti da polmonite da SARS-CoV-2
    A.3.2Name or abbreviated title of the trial where available
    RESCAT
    RESCAT
    A.4.1Sponsor's protocol code numberRESCAT
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAZIENDA OSPEDALIERO-UNIVERSITARIA DI MODENA
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportRichiesta finanziamento Bando COVID MINISTERO DELLA SALUTE, Autofinanziamento
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAzienda Ospedaliero-Universitaria Policlinico di Modena
    B.5.2Functional name of contact pointProf. Massimo Dominici
    B.5.3 Address:
    B.5.3.1Street AddressVia del Pozzo, 71
    B.5.3.2Town/ cityModena
    B.5.3.3Post code41124
    B.5.3.4CountryItaly
    B.5.4Telephone number0594222858
    B.5.6E-mailmdominici@unimore.it
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namecellule adipose perivascolari stromali mesenchimali
    D.3.2Product code [RR002]
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeRR002
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1000000 to 1500000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namecellule stromali mesenchimali da midollo osseo
    D.3.2Product code [CFM-1-BM-MSC]
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeCFM-1-BM-MSC
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1000000 to 1500000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namecellule stromali mesenchimali da sangue di cordone ombelicale
    D.3.2Product code [CF-CB-MSC]
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeCF-CB-MSC
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1000000 to 1500000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namecellule stromali mesenchimali da midollo osseo
    D.3.2Product code [PTC-MSC-TP]
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codePTC-MSC-TP
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1000000 to 1500000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namecellule stromali mesenchimali da cordone ombelicale
    D.3.2Product code [UC-MSC]
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeUC-MSC
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1000000 to 1500000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    SARS-CoV-2 pneumonia
    Polmonite da SARS-CoV-2
    E.1.1.1Medical condition in easily understood language
    COVID-19 pneumonia
    Polmonite da COVID-19
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 22.1
    E.1.2Level LLT
    E.1.2Classification code 10061229
    E.1.2Term Lung infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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
    Valutazione della fattibilità e della sicurezza dell’impiego di cellule stromali mesenchimali (MSC) allogeniche per il trattamento della polmonite severa da infezione da SARS-CoV-2 attraverso la capacità di trattare tutti i pazienti arruolati e il monitoraggio della quota di eventi avversi
    E.2.2Secondary objectives of the trial
    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.
    Valutazione dell’efficacia di MSC in termini di:
    mortalità
    andamento di PaO2/FiO2 giornaliero
    valutazione del tempo all’intubazione
    tempo all’indipendenza dalla ventilazione meccanica non invasiva
    tempo all’indipendenza dall’ossigeno-terapia
    durata ospedalizzazione
    risposta radiologica

    Valutazione di: rapporto tra conte assolute di polimorfonucleati neutrofili e linfociti, conta piastrinica, volume piastrinico, proteina C-reattiva, ferritinemia, procalcitonina, LDH, fibrinogeno, D-dimero.

    Valutazione del pattern citochinico e profilo immunofenotipico cellulare su campioni di liquido di lavaggio broncoalveolare, e di sangue periferico per definire i meccanismi patogenetici del danno in corso di COVID-19 e il meccanismo d’azione delle MSC in questo specifico setting clinico.

    Stabilire quale sia tra le tipologie di IMP utilizzati, stratificati in base all’origine tissutale delle MSC, quello associato a miglior risultato in termini di sicurezza ed efficacia.
    E.2.3Trial contains a sub-study No
    E.3Principal 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 <3,
    • Absence of known active malignancy.
    Pazienti adulti ricoverati in COVID Unit intensive e semi-intensive a causa della necessità di supporto ventilatorio per polmonite da SARS-CoV-2.
    • Firma del consenso informato,
    • Pazienti di entrambi i generi, di età compresa tra 18 e gli 80 anni (incluse),
    • Pazienti con una diagnosi virologica di infezione da SARS-CoV-2 confermata mediante real time-Polymerase Chain Reaction,
    • Ospedalizzazione per diagnosi clinica e radiologica di polmonite,
    • Valore di PaO2/FiO2 compreso tra 150-300 tale da richiedere ossigenoterapia e indicazione a supporto respiratorio non invasivo tramite CPAP (positive pressure respiratory) o ventilatorio tramite NPSV (nasal pressure support ventilation),
    • Pressione arteriosa sistolica >90 mm Hg in assenza di supporto aminico,
    • Modified Early Warning Score (MEWS) <3,
    • Assenza di neoplasia attive note.
    E.4Principal 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.
    • Non volontà a dare il consenso,
    • Storia nota di abuso alcolico o di stupefacenti nei 12 mesi precedenti l’inclusione,
    • Presenza di comorbidità significative, come ipertensione arteriosa incontrollata, patologie psichiatriche o neurologiche invalidanti, insufficienza d’organo (insufficienza renale definite come valore di clearance della creatinine al di sotto di 50 ml/min o da un valore di creatinine sierica =2.0 mg/dl; insufficienza epatica definite da un valore di bilirubina totale =2.0 mg/dl e di AST + ALT = 2.5 x il valore massimo normale; insufficienza cardiaca definite da una frazione di eiezione =40%), o qualunque altra condizione clinica rilevante, come stabilito dal Principal Investigator,
    • Presenza di malattie cardio-polmonari croniche avanzate, come ILD (pneumopatia ostruttiva, fibrosi interstiziale polmonare, proteinosi alveolare, alveolite allergica),
    • Pazienti con anormalità elettrocardiografiche clinicamente rilevanti, come stabilito dal Principal Investigator,
    • Pre-esistente patologia trombo-embolica,
    • Neoplasia attiva nota,
    • Pazienti con anamnesi positiva per reazione allergica severa (ad esempio, gonfiore della bocca e della gola, difficoltà respiratorie, ipotensione, o shock) che hanno richiesto intervento medico,
    • Pazienti con test positive per virus dell’immunodeficienza umana o epatite B o C attiva o tubercolosi o qualunque altra infezione virale (virus influenzali, adenovirus e altri virus respiratori),
    • Pazienti in stato di gravidanza, o con test di gravidanza positive, o in allattamento,
    • Pazienti che hanno subito interventi chirurgici maggiori, sia open sia per via laparoscopica, entro i 3 mesi prima dello screening,
    • Precedente trapianto di cellule staminali emopoietiche,
    • Pazienti in terapia immunosoppressiva,
    • Pazienti che stanno ricevendo o che hanno ricevuto entro 2 mesi prima dell’arruolamento in questo studio clinico, qualunque altra terapia sperimentale.
    E.5 End points
    E.5.1Primary 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, intensity, and possible association with the treatment under study. More in depth, the absolute number/percentage of Suspected Unexpected Sever Adverse Reactions (SUSARs) and Severe Adverse Reactions (SARs) recorded after 2 and 4 weeks from the MSC treatment that will not exceed 10% will be considered the cutoff to be met.
    La fattibilità verrà valutata attraverso la valutazione della capacità di produzione da parte delle Cell Factory partecipanti allo studio di un’adeguata quantità di lotti di prodotto cellulare sufficienti a trattare il 100% dei pazienti reclutati. Inoltre, verrà validato il processo di trasferimento del prodotto cellulare presso l’Unità Clinica di impiego, affinché siano garantiti tutti i requisiti di qualità, sicurezza e proprietà terapeutiche con particolare riferimento al mantenimento della vitalità dello stesso. Verrà, infine, implementato un protocollo di impiego al letto del paziente che rispetti le Good Clinical Practice, incluse le dovute misure di contenimento.
    La sicurezza verrà valutata mediante la registrazione di tutti gli eventi avversi come codificato dal¿Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0, sulla base della durata, intensità, e possibile associazione con il trattamento oggetto dello studio. In particolare, si terrà conto del numero assoluto/percentuale di Suspected Unexpected Sever Adverse Reactions (SUSAR) e di Severe Adverse Reactions (SAR) registrate nel corso del trial a 2 e 4 settimane dal trattamento con MSC che non devono superare il limite del 10%.
    E.5.1.1Timepoint(s) of evaluation of this end point
    End points will be assessed at 4 hours, 48 ¿¿hours, 7, 14, 28 and 180 days from the end of treatment or enrollment, as appropriate
    Gli end point verranno valutati a 4 ore, 48 ore, 7, 14, 28 e 180 giorni dal termine del trattamento o dall’arruolamento, come appropriato
    E.5.2Secondary 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.
    L’efficacia verrà testata mediante la valutazione di:
    a) mortalità (%) a 2 e 4 settimane,
    b) percentuale di variazione del rapporto PaO2/FiO2 quotidiano rispetto al basale,
    c) percentuale di pazienti in ventilazione invasiva meccanica,
    d) giorni in ventilazione meccanica non invasiva,
    e) giorni in ossigenoterapia,
    f) risposta radiologica
    g) giorni di ospedalizzazione
    h) percentuale di cambio di score radiologico rispetto al basale; Variazione dei parametri di laboratorio (rapporto tra conte assolute di polimorfonucleati neutrofili e linfociti, conta piastrinica, volume piastrinico, proteina C-reattiva, ferritinemia, procalcitonina, LDH, fibrinogeno, D-dimero).; Modifiche del pattern citochinico e del profilo immunofenotipico cellulare su campioni di BAL e sangue periferico, valutati tramite ELISA, citofluorimetria e single cell RNAseq, prima e dopo 1 e 2 settimane di follow-up rispetto al basale; Prevediamo di trattare un gruppo di 10 casi con MSC da cordone ombelicale, un gruppo di 10 casi con MSC da sangue di cordone ombelicale, un gruppo di 10 casi con MSC da midollo e un gruppo di 10 casi con MSC da tessuto adiposo. Valuteremo il confronto percentuale del numero totale di eventi avversi, SUSAR e SAR relati al trattamento, unitamente ai parametri di efficacia registrati a seguito dell’impiego dei diversi IMP nei vari gruppi
    E.5.2.1Timepoint(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
    Gli obiettivi verranno valutati a 4 ore, 48 ore, 7, 14, e 28 giorni dal termine del trattamento o dall’arruolamento, come appropriato; Gli end point verranno valutati dopo 2 e 4 settimane dal termine del trattamento; Gli end point verranno valutati dopo 1 e 2 settimane dal termine del trattamento; Gli end point verranno valutati a 4 ore, 48 ore, 7, 14, 28 e 180 giorni dal termine del trattamento o dall’arruolamento
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Feasibility
    Fattibilità
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Terapia standard
    Standard of care
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months12
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation Yes
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Informed consent for participation in the study (consent can be oral if a written consent cannot be expressed) will be collected before the enrollment. If the patient is unable of giving an informed consent and an authorized representative is not ava
    è prevista la firma del consenso informato ma il consenso potrebbe essere anche orale nel caso in cui quello scritto non possa essere espresso. Se il paziente non è in grado di fornire un consenso informato e un rappresentante legale non è disponibil
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 60
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients enrolled into the study possess a disease severity for which no standard of care exists. Patients will be allowed to continue receiving routine symptomatic and supportive care and current therapy according to clinical judgment.
    I pazienti arruolati nello studio sono affetti da una patologia per la quale non esiste uno standard di cura. I pazienti continueranno a ricevere cure sintomatiche e di supporto di routine e terapia corrente secondo il giudizio clinico
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-10-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-12-28
    P. End of Trial
    P.End of Trial StatusOngoing
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