E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe viral lung infections |
Infecciones pulmonares víricas graves |
|
E.1.1.1 | Medical condition in easily understood language |
Severe viral lung infections |
Infecciones pulmonares víricas graves |
|
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 |
Evaluar la eficacia de tozorakimab frente a placebo como complemento al tratamiento estándar en pacientes con infección pulmonar vírica que requieren suplemento de oxígeno en la prevención de la muerte o progresión a ventilación mecánica invasiva (IMV/ECMO) el día 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. Evaluar la eficacia de tozorakimab frente a placebo como complemento al tratamiento estándar sobre:
a) la mortalidad por cualquier causa el día 60
b) la estancia en la en la unidad de cuidados intensivos (UCI)
c) la duración del suplemento de oxígeno
d) la prolongación del tiempo hasta la muerte o IMV/ECMO
e) la prolongación del tiempo hasta la muerte
f) el uso de ventilación asistida
g) el ingreso en la UCI
h) la duración de la hospitalización
i) el estado clínico evaluado por el investigador utilizando la escala de progresión clínica ordinal de 10 categorías de la OMS el día 60.
2. Evaluar la farmacocinéticay la inmunogenicidad de tozorakimab.
3. Evaluar el uso de los niveles basales de biomarcadores séricos para predecir la respuesta al tratamiento con tozorakimab frente a placebo como complemento al tratamiento estándar.
4. Evaluar la seguridad y tolerabilidad de tozorakimab frente a placebo como complemento al tratamiento estándar. |
|
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. Pacientes adultos ≥ 18 años en el momento de firma del consentimiento informado.
2. Pacientes hospitalizados con infección pulmonar vírica.
3. Hipoxemia que requiere tratamiento con suplemento de oxígeno. |
|
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. Infección pulmonar fúngica o parasitaria conocida, infección pulmonar por aspiración, absceso pulmonar o sepsis pulmonar. Se permite la coinfección bacteriana, a menos que, a juicio del investigador, la infección bacteriana defina la gravedad del estado del paciente.
2. Hipoxemia causada principalmente por lesión extrapulmonar o por lesión pulmonar de etiología no infecciosa.
3. IMV/ECMO en curso o inminente en la aleatorización. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants who die or progress to IMV/ECMO |
Proporción de pacientes que mueren o progresan a IMV/ECMO |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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. Incidence of anti-drug antibodies
16. Baseline serum biomarker levels relative to primary endpoint |
1. Proporción de participantes que mueren
2. Número de días de superviencia y fuera de la UCI
3. Número de días de supervivencia y sin oxígeno suplementario
4. Tiempo hasta la muerte o progresión a IMV/ECMO
5. Proporción de pacientes que mueren o progresan a IMV/ECMO
6. Tiempo hasta la muerte (todas las causas)
7. Proporción de pacientes que mueren
8. Número de días de supervivencia y libre de IMV/ECMO
9. Número de días de supervivencia y sin respiración asistida
10. Proporción de pacientes con ingreso en UCI o muerte
11. Proporción de pacientes vivos y dados de alta de hospitalización
12. Hora del alta de hospitalización
13.Hora de retirada del suplemento de oxígeno
14. Comparación basada en el rango de puntuación de la CPS de la OMS
15. Incidencia de anticuerpos antifármacos
16.Niveles basales de biomarcadores séricos en relación con el criterio principal de evaluación |
|
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
14. NA
15. NA
16. NA |
1. En el día 60
2. Durante un periodo de 60 días
3. Durante un periodo de 60 días
4. NA
5. En el día 28
6.NA
7. En el día 28
8. Durante un periodo de 60 días
9. Durante un periodo de 60 días
10. En el día 28 y en el día 60
11. En el día 28 y en el día 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 | 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 |
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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |