E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe COVID-19 pneumonia |
NEUMONÍA GRAVE POR EL COVID-19 |
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E.1.1.1 | Medical condition in easily understood language |
Severe COVID-19 pneumonia |
NEUMONÍA GRAVE POR EL COVID-19 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
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 |
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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 |
The primary objective for this study is to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of TCZ compared with placebo in combination with SOC for the treatment of severe COVID-19 pneumonia |
El objetivo principal de este estudio es evaluar la eficacia, seguridad, farmacodinámica y farmacocinética de tocilizumab (TCZ) en comparación con el placebo correspondiente en combinación con el tratamiento estándar (TE) en pacientes hospitalizados con neumonía grave por COVID-19 |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years
- Hospitalized with COVID-19 pneumonia confirmed per WHO criteria (including a positive PCR of any specimen; e.g., respiratory, blood, urine, stool, other bodily fluid) and evidenced by chest X-ray or CT scan
- SpO2 <= 93% or PaO2/FiO2 < 300 mmHg. |
-Edad ≥18 años
- Hospitalizado con neumonía de la COVID-19 confirmada según los criterios de la OMS (incluida una RCP positiva de cualquier muestra; p. ej., respiratoria, sangre, orina, heces, otro líquido corporal) y mediante radiografía de tórax o TAC
-SpO2 ≤93 % o PaO2/FiO2 <300 mmhg |
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E.4 | Principal exclusion criteria |
- Known severe allergic reactions to TCZ or other monoclonal antibodies
- Active TB infection
- Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
- In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
- Have received oral anti-rejection or immunomodulatory drugs (including tocilizumab) within past 6 months
- Pregnant or lactating women
- Participating in other drug clinical trials (with possible exception of anti-viral trials)
- ANC < 1000/mm3
- Platelet count < 50,000/mm3
- ALT or AST > 10 x ULN
- Treatment with an investigational drug within 5 half-lives or 30 days
- 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. |
-Reacciones alérgicas graves conocidas a TCZ u otros anticuerpos monoclonales
-Infección por tuberculosis activa
-Sospecha de infección bacteriana, fúngica, vírica u otra infección (además de COVID-19)
- En opinión del investigador, la progresión a la muerte es inminente e inevitable en las próximas 24 horas, independientemente de la administración de tratamientos
-Haber recibido fármacos antirrechazo orales o inmunomoduladores (incluido TCZ) en los últimos 6 meses
-Embarazo o lactancia, o prueba de embarazo positiva en un examen previo a la dosis
-Participación en otros ensayos clínicos con fármacos (con posible excepción de ensayos antivirales)
-(RAN) <1000/µl en la visita de selección
- Recuento de plaquetas <50 000/µl
-ALT o AST >10 x LSN
-Tratamiento con un fármaco en investigación en las 5 semividas o 30 días
-Cualquier afección médica grave o anomalía en pruebas analíticas clínicas que, a juicio del investigador, impidan la participación segura del paciente y la realización del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is Clinical status assessed using a 7-category ordinal scale. |
El objetivo principal de eficacia es la evaluación del estado clínico mediante una escala ordinal de 7 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
• Time to clinical improvement
• Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
• Incidence of mechanical ventilation
• Ventilator-free days
• Organ failure-free
• Incidence of intensive care unit (ICU) stay
• Duration of ICU stay
• Time to clinical failure, defined as the time to death, mechanical ventilation, ICU admission, or withdrawal
• Mortality rate
• Time to hospital discharge or “ready for discharge”
• Duration of supplemental oxygen. |
Los secondary endponts son:
• Tiempo hasta la mejoría clínica.
• Tiempo hasta la mejora clínica de al menos 2 categorías con respecto al inicio en una escala ordinal de 7 categorías del estado clínico
• Incidencia de ventilación mecánica.
• Días sin ventilador.
• Días sin fallo orgánico
• Incidencia de estancia en la unidad de cuidados intensivos (UCI)
• Duración de la estancia en la UCI
• Tiempo hasta el fracaso clínico, definido como el tiempo hasta la muerte, la ventilación mecánica, el
ingreso en la UCI o la retirada
• Tasa de mortalidad
• Tiempo hasta el alta hospitalaria o “listo para el alta”
• Duración del oxígeno suplementario. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At time points throughout the study |
En puntos temporales especificados a lo largo del estudio |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Denmark |
France |
Germany |
Ireland |
Italy |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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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
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The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later.
In addition, the Sponsor may decide to terminate the study at any time. |
El final de este estudio se define como la fecha en la que tenga lugar la última visita del último paciente, o la fecha en la que se recibe el último punto de datos necesarios para el último seguimiento del último paciente, lo que ocurra más tarde.
Además, el promotor podrá decidir poner fin al estudio en cualquier momento |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |