E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19-induced pneumonia (CAN-COVID) |
COVID-19-neumonía inducida (CAN-COVID). |
|
E.1.1.1 | Medical condition in easily understood language |
COVID-19-induced pneumonia (CAN-COVID) |
COVID-19-neumonía inducida (CAN-COVID). |
|
E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053983 |
E.1.2 | Term | Corona virus infection |
E.1.2 | System Organ Class | 100000004862 |
|
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 demonstrate the benefit of canakinumab + SOC in increasing chance of survival without ever requiring invasive mechanical ventilation among patients with COVID-19-induced pneumonia and CRS. |
Demostrar el beneficio de canakinumab + SOC en el aumento de la probabilidad de supervivencia sin haber requerido ventilación mecánica invasiva entre los pacientes con neumonía inducida por COVID-19 y SLC. |
|
E.2.2 | Secondary objectives of the trial |
- To demonstrate the benefit of canakinumab in reducing 4-week case fatality rate (CFR) among patients with COVID-19-induced pneumonia and CRS regardless of other subsequent clinical interventions - To evaluate change in clinical serologic measurements related to CRS in COVID-19 patients with pneumonia - To evaluate safety of canakinumab in patients with COVID-19-induced pneumonia and CRS. |
-Demostrar el beneficio de canakinumab en la reducción de la tasa de letalidad (TL) a las 4 semanas entre los pacientes con neumonía inducida por COVID-19 y SLC, independientemente de otras intervenciones clínicas posteriores. -Evaluar el cambio respecto a la basal en las mediciones serológicas clínicas relacionadas con el SLC en pacientes con neumonía por COVID-19. - Evaluar la seguridad de canakinumab en pacientes con neumonía inducida por COVID-19 y SLC. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female 2.Adults (>= 18 years old) 3.Body weight >= 40 kg 4.Informed consent must be obtained prior to participation in this study. 5.Clinically diagnosed with SARS-CoV-2 virus by PCR or by other approved diagnostic methodology within 7 days prior to randomization 6.Hospitalized with COVID-19-induced pneumonia evidenced by chest x-ray or CT scan (taken within 5 days prior to randomization) with pulmonary infiltrates 7.SpO2 <= 93% on room air or arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m)) 8.C-reactive protein >= 20 mg/L or ferritin level >= 600 µg/L |
1. Hombres o mujeres. 2. Adultos (>=18 años de edad). 3. Peso corporal >=40 kg. 4. Se deberá obtener el consentimiento informado antes de la participación en este estudio. 5. Presentar diagnóstico clínico de enfermedad por virus SARS-CoV-2 mediante PCR u otro método diagnóstico aprobado durante los 7 días anteriores a la aleatorización. 6. Hospitalización por neumonía inducida por COVID-19 evidenciada por radiografía de tórax o TC (realizada durante los 5 días anteriores a la aleatorización) con infiltrados pulmonares. 7. SpO2 <= 93 % respirando aire ambiente o presión parcial de oxígeno arterial (PaO2)/fracción de oxígeno inspirado (FiO2) <300 mmHg (1 mmHg = 0,133 kPa) (debe utilizarse la formulación correctiva para regiones de mayor altitud [más de 1000 m]). 8. Proteína C reactiva>=20 mg/l o nivel de ferritina >=600 μg/l. |
|
E.4 | Principal exclusion criteria |
1.History of hypersensitivity to canakinumab or to biologic drugs 2.Intubated and on mechanical ventilation (invasive) at time of randomization 3.Treatment with biologic immunomodulators or immunosuppressant drugs, including but not limited to anakinra, tocilizumab, TNF inhibitors and anti-IL-17 agents within 5 half-lives prior to randomization. Note: Immunomodulators (topical or inhaled) for asthma and atopic dermatitis and corticosteroids are not restricted. 4.Suspected or known untreated active bacterial, fungal, viral, or parasitic infection with the exception of COVID-19 5.Neutropenia with ANC <1000/mm3 6.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 7.In the opinion of the investigator, progression to death is imminent and highly likely within the next 24 hours, irrespective of the provision of treatments 8.Current participation in any other investigational trials. |
1. Antecedentes de hipersensibilidad a canakinumab o a fármacos biológicos. 2. Intubación o uso de ventilación mecánica (invasiva) en el momento de la aleatorización. 3. Tratamiento con inmunomoduladores o fármacos inmunosupresores, que incluyen entre otros tocilizumab, inhibidores de TNF y fármacos anti-IL-17, durante las 5 vidas medias o 30 días (aquel periodo que sea más largo) anteriores a la aleatorización, excepto anakinra que se excluye solo durante las 5 vidas medias anteriores. Nota: se permite el uso de inmunomoduladores (tópicos o inhalados) para el asma y la dermatitis atópica y el uso de corticosteroides (cualquier vía de administración). 4. Sospecha o conocimiento de infección bacteriana, por hongos, vírica o parasitaria activa y no tratada, salvo la infección por COVID-19. 5. Neutropenia con RAN <1000/mm3. 6. Cualquier enfermedad grave o anomalía en las pruebas analíticas que, según el criterio del investigador, impida una participación segura del paciente en el estudio así como su finalización. 7. Según el investigador, la progresión a la muerte es inminente y muy probable durante las siguientes 24 horas, independientemente de la administración de tratamientos. 8. Participación actual en cualquier otro ensayo en investigación. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Clinical response, defined as survival without ever requiring invasive mechanical ventilation from Day 3 (inclusive) up to Day 29 (inclusive). |
Respuesta clínica, definida como supervivencia sin necesidad de ventilación mecánica invasiva desde el día 3 (inclusive) hasta el día 29 (inclusive). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- COVID-19-related death during the 4-week period after study treatment - Adjusted geometric mean ratio to baseline overtime up to Day 29 in the following clinical chemistry measurements: - CRP - Serum ferritin - D-dimer - Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs. |
- Muerte relacionada con COVID-19 durante el período de 4 semanas después del tratamiento del estudio Relación geométrica media ajustada desde la basal hasta el día 29 en las siguientes mediciones de química clínica: -PCR -Suero de ferritina -dímero D - Número de pacientes con acontecimientos adversos (EA), acontecimientos adversos graves (SAE), cambios clínicamente significativos en las medidas de laboratorio y signos vitales. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Duration of trial |
Duración del ensayo |
|
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 | 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) | 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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
|
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
|
LVLS |
LVLS Última visita última paciente |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 6 |
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 |