E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe COVID-19 pneumonia |
Polmonite grave da COVID-19 |
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E.1.1.1 | Medical condition in easily understood language |
Severe COVID-19 pneumonia |
Polmonite grave da 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 |
L’obiettivo primario di questo studio consiste nel valutare l’efficacia, la sicurezza, la farmacocinetica e la farmacodinamica di TCZ rispetto a placebo in combinazione con lo standard di cura (Standard Of Care, [SOC]) per il trattamento della polmonite grave da 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. |
- Età >= 18 anni - Pazienti ricoverati in ospedale affetti da polmonite da COVID-19 confermata secondo i criteri dell’Organizzazione Mondiale della Sanità (OMS) (inclusa una reazione a catena della polimerasi [Polymerase Chain Reaction, (PCR)] positiva di qualsiasi campione biologico, per es. prelevato dalle vie respiratorie, sangue, urine, feci, altri liquidi corporei) ed evidenziata mediante radiografia o tomografia computerizzata (TC) del torace - Saturazione di ossigeno dell’emoglobina presente nel sangue (SpO2) <= 93% o rapporto tra pressione parziale dell’ossigeno nel sangue / frazione di ossigeno nell’aria inspirata (Arterial Oxygen Partial Pressure to Fractional Inspired Oxygen, [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. |
- Reazioni allergiche gravi note a TCZ o altri anticorpi monoclonali - Sospetta infezione tubercolare (TB) attiva - Sospetta infezione batterica, micotica, virale o altra infezione attiva (oltre all’infezione da COVID-19) - Secondo l’opinione dello sperimentatore, la progressione al decesso è imminente e, pertanto, inevitabile entro le 24 ore successive, indipendentemente dalla somministrazione di trattamenti - Avere ricevuto farmaci antirigetto o immunomodulatori per via orale (compreso tocilizumab) negli ultimi 6 mesi - Donne in gravidanza o che allattano al seno - Partecipazione ad altre sperimentazioni cliniche di medicinali (con possibile eccezione delle sperimentazioni di farmaci antivirali) - Conta assoluta dei neutrofili (Absolute Neutrophil Count, [ANC]) < 1.000/mm - Conta piastrinica < 50.000/mm3 Alanina aminotransferasi (ALT) o aspartato aminotransferasi (AST) > 10 volte il limite superiore della norma (Upper Limit of Normal, [ULN]) - Trattamento con un farmaco sperimentale entro 5 emivite o 30 giorni - Qualsiasi condizione medica seria o anomalia ai test clinici di laboratorio che, a giudizio dello sperimentatore, precluda la partecipazione sicura allo studio e il completamento dello stesso da parte del/la paziente. |
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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.
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L’endpoint di efficacia primario è costituito dallo stato clinico valutato utilizzando una scala ordinale a 7 categorie. |
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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. |
Gli endpoint di efficacia secondari sono: • Tempo al miglioramento clinico • Tempo al miglioramento di almeno 2 categorie rispetto al basale su una scala ordinale a 7 categorie di valutazione dello stato clinico • Incidenza della ventilazione meccanica • Giorni senza utilizzo del ventilatore • Assenza di insufficienza d’organo • Incidenza della degenza in unità di terapia intensiva (UTI) • Durata della degenza in UTI • Tempo al fallimento clinico, definito come il tempo trascorso fino al decesso, alla ventilazione meccanica, al ricovero ospedaliero in UTI o al ritiro • Tasso di mortalità • Tempo alla dimissione dall’ospedale o alla condizione di paziente “pronto/a per la dimissione” • Durata della supplementazione di ossigeno. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At time points throughout the study |
Ai diversi punti dello studio |
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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 | 5 |
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. |
La conclusione di questo studio è definita come la data in cui si verifica l’ultima visita dell’ultimo/a paziente (Last Patient Last Visit, [LPLV]) o la data in cui si ottiene dall’ultimo/a paziente l’ultimo punto dati richiesto per l’analisi statistica o il follow-up di sicurezza, a seconda di quale evento si verifichi più tardi. Inoltre, lo sponsor potrà decidere di concludere lo studio in qualsiasi 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 |