E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe COVID-19 pneumonia |
Neumonía severa por COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
Coronavirus pneumonia |
Neumonía por coronavirus |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070255 |
E.1.2 | Term | Coronavirus test positive |
E.1.2 | System Organ Class | 10022891 - Investigations |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10035737 |
E.1.2 | Term | Pneumonia viral |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and efficacy of the administration of two doses of Allogeneic Adipose Tissue-derived Mesenchymal Stem Cells in severe or critical pneumonia caused by COVID-19 infection |
Evaluar la seguridad y eficacia de la administración de dos dosis de células mesenquimales troncales adultas alogénicas de tejido adiposo expandidas en neumonía severa o crítica causada por la infección de COVID-19 |
|
E.2.2 | Secondary objectives of the trial |
To assess the immunomodulatory effects of MSC against the control group through changes in immune markers, using flow cytometry, collecting samples on days 1, 3, 6, and 15 days after administration of the investigational therapy.
To study the expression of coronavirus receptors in mesenchymal cells through the analysis of gene expression of the angiotensin convertase-2 enzyme (ACE-2 or ACE2) and the TMPRSS2 protease used by SARS-CoV-2 as a gateway to the alveolar cell |
Evaluar de los efectos inmunomoduladores de MSC frente al grupo control a través de los cambios de los marcadores inmunes, mediante citometría de flujo, recogiéndose muestras los días 1, 3, 6, y 15 días después de la administración de la terapia en investigación. Estudiar la expresión de receptores del coronavirus en las células mesenquimales a través del análisis de la expresión génica de la enzima convertasa de la angiotensina – 2 (ECA-2 o ACE2) y la proteasa TMPRSS2 empleados por el SARS-CoV-2 como puerta de entrada a la célula alveolar |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 2. Clinical diagnosis of Pneumonia, severe or critical, caused by COVID-19 infection 3. Life expectancy > 48 hours. 4. Commitment to use a contraceptive method of proven efficacy in both men and women during the duration of the clinical trial. |
1. Edad ≥ 18 2. Diagnóstico clínico de Neumonía, severa o crítica, causada por infección por COVID-19 3. Expectativa de vida superior a 48 horas. 4. Compromiso de utilización de un método anticonceptivo de eficacia probada tanto en hombres como en mujeres durante la duración del ensayo clínico. |
|
E.4 | Principal exclusion criteria |
1. Coinfection with other viruses or bacteria (HIV, tuberculosis, influenza virus, adenovirus or other respiratory infections, active infection by HBV or C). 2. History of multiple allergies, including allergy to Penicillin or other B-lactams. 3. Pregnant and lactating women. 4. Patients with malignant tumors or hemopathies or any state of immunosuppression considered as severe. 5. Patients with autoimmune diseases. 6. Chronic heart failure with ejection fraction less than 30%. 7. Any other condition for which, in the opinion of the main investigator, the subject is considered not to be in compliance with the study. |
1. Coinfección con otros virus o bacterias (HIV, tuberculosis, virus influenza, adenovirus u otras infecciones respiratorias, infección activa por VHB o C). 2. Historial de múltiples alergias, incluyendo alergia a Penicilina u otros B-lactámicos. 3. Mujeres embarazadas y lactantes. 4. Pacientes con tumores malignos o hemopatías o cualquier estado de inmunosupresión considerado como grave. 5. Pacientes con enfermedades autoinmunes. 6. Insuficiencia cardíaca crónica con fracción de eyección inferior al 30%. 7. Cualquier otra condición por la que, a juicio del investigador principal, se considere que el sujeto no se ajusta al estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety endpoints: Incidence of Adverse Events and Serious Adverse Events, related to the investigational drug or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE). Efficacy endpoints: Reduction of the SARS-CoV-2 viral load by PCR on days 6 and 15. Mortality at day 15. Mortality at day 28. Proportion of patients in categories 5, 6 or 7 of the ordinal scale of 7 points on days 15 and 28 days Proportion of patients needing rescue therapy (Tocilizumab, corticosteroids, or therapies under investigation in clinical trials) Time to get an improvement in a category since admission to the ordinal scale. |
Variables de seguridad: Incidencia de Acontecimientos Adversos y Acontecimientos Adversos Graves, relacionados con el medicamento en investigación o con el procedimiento de administración, graduados según la escala de common toxicity criteria (CTCAE). Variables de eficacia: Reducción de la carga viral SARS-CoV-2 por PCR en los días 6 y15 . Mortalidad a día 15. Mortalidad a día 28. Proporción de pacientes en las categorías 5, 6 o 7 de la escala ordinal de 7 puntos a día 15 y 28 días Escala ordinal: 1. No hospitalizado, sin limitaciones en las actividades. 2. No hospitalizado, limitaciones en las actividades. 3. Hospitalizado, sin requerimiento de suplemento de oxígeno. 4. Hospitalizado, con requerimiento de suplemento de oxígeno. 5. Hospitalizado, con ventilación no invasiva o dispositivo de alto flujo de oxígeno o mascarilla de oxígeno con reservorio). 6. Hospitalizado, con ventilación mecánica invasiva o ECMO. 7. Muerte. Proporción de pacientes que necesitan recibir terapia de rescate (Tocilizumab, corticosteroides o terapias en fase de investigación en ensayos clínicos) Tiempo en obtener una mejoría en una categoría desde la admisión en la escala ordinal. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
For safety: 12 months post-infusión For efficacy: At baseline and at 1, 3, 6, 9, 15, 21 and 28 days after infusion, acording to the visits and assessments schedule of the trial protocol. |
Seguridad: 12 meses post-infusión Eficacia: Basal y a los 1, 3, 6, 9, 15,21 y 28 días tras la infusión, conforme al calendario de visitas e evaluaciones del protocolo del estudio. |
|
E.5.2 | Secondary end point(s) |
Prior to MSC treatment, an aliquot will be obtained that will be cryopreserved at UPCIT, to subsequently carry out a study of the possible expression of coronavirus receptors in mesenchymal cells:It will analyze the gene expression of the angiotensin convertase enzyme - 2. (ECA-2 or ACE2) and the TMPRSS2 protease used by SARS-CoV-2 as a gateway to the alveolar cell. |
Previo al tratamiento con las MSC, se obtendrá una alícuota que será criopreservada en la UPCIT, para posteriormente realizar un estudio de la posible expresión de receptores del coronavirus en las células mesenquimales: Se analizará la expresión génica de la enzima convertasa de la angiotensina – 2 (ECA-2 o ACE2) y la proteasa TMPRSS2 empleados por el SARS-CoV-2 como puerta de entrada a la célula alveolar. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At day 1 and 3, prior to infusion. |
Se analizarán las muestras tomadas del día 1 y 3 antes de la infusión. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Tratamiento clínico establecido para COVID-19 |
Treatment according to clinical practice By COVID-19 |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial 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
|
Last visit of the last subjet |
Última visita del último paciente incluido |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |