E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe viral lung infections |
Infezioni polmonari virali severe |
|
E.1.1.1 | Medical condition in easily understood language |
Severe viral lung infections |
Infezioni polmonari virali severe |
|
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 | 10001053 |
E.1.2 | Term | Acute respiratory failure |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
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 effect of tozorakimab versus placebo as add on to SoC in participants with viral lung infection requiring supplemental oxygen on the prevention of death or progression to IMV/ECMO by Day 60 |
Valutare l’effetto di tozorakimab, rispetto al placebo, come terapia aggiuntiva rispetto alla SoC nei partecipanti con infezione polmonare virale che richiede ossigeno supplementare, sulla prevenzione del decesso o della progressione a IMV/ECMO entro il Giorno 60 |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of tozorakimab versus placebo as add-on to standard of care on:
a) all-cause mortality by Day 60 b) ICU stay c) duration of oxygen supplementation d) prolonging time to death or IMV/ECMO e) prolonging time to death f) ventilator use g) ICU admissions h) duration of hospitalisation i) clinical status as assessed by the Investigator using WHO 10-category ordinal Clinical Progression Scale by Day 60.
2. To evaluate the pharmacokinetics and immunogenicity of tozorakimab.
3. To evaluate the use of baseline serum biomarker levels to predict treatment response with tozorakimab versus placebo as add on to standard of care.
4. To assess the safety and tolerability of tozorakimab versus placebo as add-on to standard of care. |
1. Valutare l’effetto di tozorakimab, rispetto al placebo, come aggiunta alla Standard of Care (SoC) su:
a) mortalità per tutte le cause entro il Giorno 60 b) permanenza nell'unità di terapia intensiva (UTI) c) durata della supplementazione di ossigeno d) prolungamento del tempo al decesso o a IMV/ECMO e) prolungamento del tempo al decesso f) uso di ventilazione g) ricoveri ospedalieri nell'UTI h) durata di ospedalizzazione i) stato clinico valutato dallo sperimentatore utilizzando la scala ordinale di progressione clinica (CPS) a 10 categorie dell’OMS entro il Giorno 60.
2. Valutare la farmacocinetica (PK) e l’immunogenicità di tozorakimab.
3. Valutare l’uso dei livelli basali di biomarcatori sierici per predire la risposta al trattamento con tozorakimab rispetto al placebo come aggiunta alla SoC.
4. Valutare la sicurezza e la tollerabilità di tozorakimab, rispetto al placebo, come aggiunta alla SoC. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult participants = 18 years old at the time of signing the informed consent form.
2. Patients hospitalised with viral lung infection.
3. Hypoxaemia requiring treatment with supplemental O2 |
1. Partecipanti adulti = 18 anni al momento della firma del modulo di consenso informato.
2. Pazienti ricoverati con infezione polmonare virale
3. Ipossiemia che richiede un trattamento supplementare con O2. |
|
E.4 | Principal exclusion criteria |
1. Known fungal or parasitic lung infection, aspiration lung infection, lung abscess, or pulmonary sepsis. Bacterial co-infection is allowed, unless, in the opinion of the investigator, bacterial infection defines the severity of the participant’s condition.
2. Hypoxaemia caused primarily by extrapulmonary insult or by lung injury of non-infective aetiology.
3. Ongoing or impending IMV/ECMO at randomisation. |
1. Infezione polmonare nota da funghi o parassiti, infezione polmonare da aspirazione, ascesso polmonare o sepsi polmonare. La coinfezione batterica è permessa, a meno che, secondo il giudizio dello sperimentatore, l'infezione batterica definisca la severità della condizione del partecipante.
2. Ipossiemia causata principalmente da insulto extrapolmonare o da lesione del polmone di eziologia non infettiva.
3. IMV/ECMO in corso o imminente alla randomizzazione. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants who die or progress to IMV/ECMO |
Proporzione di partecipanti che muore o progredisce a IMV/ECMO |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
By Day 60 |
Entro il giorno 60 |
|
E.5.2 | Secondary end point(s) |
1. Proportion of participants who die 2. Number of days alive and outside of ICU 3. Number of days alive and free of supplemental oxygen 4. Time to death or progression to IMV/ECMO 5. Proportion of participants who die or progress to IMV/ECMO 6. Time to death (all cause) 7. Proportion of participants who die 8. Number of days alive and free of IMV/ECMO 9. Number of days alive and ventilator free 10. Proportion of participants with ICU admission or death 11. Proportion of participants alive and discharged 12. Time to discharge 13. Time to being off supplemental oxygen 14. WHO CPS score rank-based comparison 15. Serum concentration of tozorakimab (pharmacokinetics) and incidence of anti-drug antibodies (immunogenicity) 16. Baseline serum biomarker levels relative to primary endpoint |
1. Proporzione di partecipanti che muore 2. Numero di giorni in vita e al di fuori dell’UTI 3. Numero di giorni in vita e senza ossigeno supplementare 4. Tempo al decesso o alla progressione a IMV/ECMO 5. Proporzione di partecipanti che muore o progredisce a IMV/ECMO 6. Tempo al decesso (tutte le cause) 7. Proporzione di partecipanti che muore 8. Numero di giorni in vita e senza IMV/ECMO 9. Numero di giorni in vita e senza uso del ventilatore 10. Proporzione di partecipanti con ricovero nell’UTI o decesso 11. Proporzione di partecipanti in vita e dimessi 12. Tempo alla dimissione 13. Tempo alla sospensione dell’ossigeno supplementare 14. Confronto basato sui ranghi della CPS dell’OMS 15. Concentrazioni sieriche di tozorakimab (farmacocinetica) e incidenza degli ADA (immunogenicità) 16. Livelli basali dei biomarcatori sierici relativi all'endpoint primario |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. By Day 60 2. Over 60 day period 3. Over 60 day period 4. NA 5. By Day 28 6. NA 7. By Day 28 8. Over 60 day period 9. Over 60 day period 10. By Day 28 and Day 60 11. By Day 28 and Day 60 12. NA 13. NA 13. NA 14. NA 15. NA 16. NA |
1. Entro il giorno 60 2. Nell'arco di un periodo di 60 giorni 3. Nell'arco di un periodo di 60 giorni 4. NA 5. Entro il giorno 28 6. NA 7. Entro il giorno 28 8. Nell'arco di un periodo di 60 giorni 9. Nell'arco di un periodo di 60 giorni 10. Entro il giorno 28 ed entro il giorno 60 11. Entro il giorno 28 ed entro il giorno 60 12. NA 13. NA 14. NA 15. NA 16. NA |
|
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 | 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 | 91 |
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 | Information not present in EudraCT |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
Colombia |
Hong Kong |
India |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Peru |
Philippines |
Saudi Arabia |
South Africa |
Taiwan |
Thailand |
United States |
Viet Nam |
Austria |
France |
Poland |
Sweden |
Bulgaria |
Netherlands |
Romania |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Denmark |
Hungary |
Slovakia |
Turkey |
United Kingdom |
|
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
|
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 6 |