E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) |
Enfermedad por coronavirus 2019 (COVID-19) |
|
E.1.1.1 | Medical condition in easily understood language |
COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most people infected with the virus experience mild to moderate respiratory illness. |
COVID-19enfermedad contagiosa causada por el síndrome respiratorio agudo severo coronavirus2.La mayoría de las personas con el virus experimentan una enfermedad respiratoria de leve-moderada. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
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 characterize the pharmacokinetics of tocilizumab (TCZ) through Day 28 |
Caracterizar la farmacocinética de TCZ hasta el día 28. |
|
E.2.2 | Secondary objectives of the trial |
- To characterize the pharmacodynamics of TCZ through Day 60 - To evaluate the safety of TCZ through Day 60 |
-Caracterizar la farmacodinamia de TCZ hasta el día 60. -Evaluar la seguridad de TCZ hasta el día 60 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Aged less than 18 years at the time of signing Informed Consent Form or Assent (if applicable) - Ability to comply with the study protocol, in the investigator's judgment - Hospitalized with COVID-19 confirmed per a positive polymerase chain reaction (PCR) of any specimen and evidenced by chest X-ray or CT scan - Receiving systemic corticosteroids at baseline - Oxygen saturation <93% on room air, or requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) to maintain oxygen saturation >92% at screening and baseline - For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs during the treatment period and for 90 days after the final dose of TCZ - For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, during the treatment period and for 60 days after the final dose of TCZ to avoid exposing the embryo |
1-Edad inferior a 18 años en el momento de firmar el documento de consentimiento informado o el asentimiento (si procede). 2-Capacidad para cumplir el protocolo del estudio, en opinión del investigador. 3-Hospitalización con COVID-19 confirmada por una PCR positiva en una muestra (por ejemplo, respiratoria, sangre, orina, heces u otro líquido corporal) y demostrada en una radiografía o TC de tórax. 4-Tratamiento con corticosteroides sistémicos en el momento basal. 5-Saturación de oxígeno <93% con aire ambiente o necesidad de oxigenoterapia, ventilación mecánica no invasiva o invasiva o ECMO para mantener una saturación de oxígeno >92% en las visitas de selección e inicial. 6-Para las participantes con capacidad reproductiva: compromiso de practicar abstinencia sexual (ausencia de relaciones heterosexuales) o utilizar métodos anticonceptivos, así como de abstenerse de donar óvulos, durante el período de tratamiento y hasta 90 días después de la última dosis de TCZ. 7-Para los varones: compromiso de practicar abstinencia sexual (abstenerse de mantener relaciones heterosexuales) o utilizar métodos anticonceptivos, así como de no donar semen, preservativo durante el período de tratamiento y hasta, como mínimo, 60 días después de la última dosis de TCZ para no exponer al embrión. |
|
E.4 | Principal exclusion criteria |
- Gestational age <37 weeks - Known severe allergic reactions to TCZ or other monoclonal antibodies - Active tuberculosis infection - Uncontrolled active bacterial, fungal, viral, or other infection (besides COVID-19) - Diagnosis or suspected diagnosis of multisystem inflammatory syndrome in children (MIS-C) - In the opinion of the investigator, progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments - Have received oral anti-rejection or immunomodulatory drugs (including TCZ) within the past 3 months prior to enrollment - Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN) detected within 24 hours of screening Platelet count <50,000/µL at screening - Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 90 days after the final dose of TCZ - Treatment with an investigational drug within 5 drug-elimination half-lives or 30 days, whichever is longer, of enrollment (except for anti-SARS-CoV-2 antibodies or directly acting antivirals) - Participating in another interventional drug clinical trial (except for anti-SARS-CoV-2 antibodies or directly acting antivirals) - 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 |
1-Edad gestacional <37 semanas. 2-Reacciones alérgicas graves conocidas a TCZ u otros anticuerpos monoclonales. 3-Infección activa por tuberculosis. 4-Infección activa no controlada por bacterias, hongos, virus u otros microorganismos (aparte de COVID-19). 5-Diagnóstico o sospecha de diagnóstico de SIMP. 6-En opinión del investigador, la progresión a la muerte es inminente e inevitable en las 48 horas siguientes, con independencia de la administración de tratamientos. 7-Haber recibido fármacos antirrechazo o inmunomoduladores por vía oral (incluido TCZ) en los 3 meses previos a la inclusión. 8-ALT o AST >10 x el límite superior de la normalidad (LSN) detectada en las 24 horas previas a la selección (según los intervalos de referencia del laboratorio local). 9-Embarazo o lactancia, o intención de quedarse embarazada durante el estudio o en los 90 días siguientes a la última dosis de TCZ (solo para las mujeres con capacidad reproductiva). 10-Tratamiento con un fármaco en investigación en el plazo de 5 semividas de eliminación del fármaco o 30 días, lo que suponga más tiempo, antes de la inclusión (excepto anticuerpos anti-SARS-CoV-2 o antivirales de acción directa). 11-Participación en otro ensayo clínico intervencionista con fármacos (excepto anticuerpos anti-SARS-CoV-2 o antivirales de acción directa). 12-Cualquier enfermedad grave o alteración analítica que, en opinión del investigador, descarte la participación segura del paciente en el estudio y su finalización. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Serum concentrations of TCZ at specified timepoints and derived PK parameters (maximal serum concentration [Cmax], area under the concentration-time curve up to Day 28 [AUCDays 0-28], serum concentration on Day 28 [CDay28], total clearance of drug [CL], and volume of distribution) |
1.Concentraciones séricas de TCZ en momentos especificados y parámetros FC derivados (Cmáx, AUCDías 0-28, CDía 28, CL y volumen de distribución). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to Day 28 |
1. Hasta el día 28 |
|
E.5.2 | Secondary end point(s) |
1. Duration of 90% saturation of soluble interleukin-6 receptor (sIL-6R) through Day 28 2. Concentrations of interleukin 6 (IL-6), sIL-6R, and C-reactive protein (CRP) at specified timepoints 3. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 grading scale 4. Incidence of serious adverse events 5. Change from baseline in targeted vital signs 6. Change from baseline in targeted clinical laboratory test results |
1.Duración de la saturación del 90 % del sIL-6R hasta el día 28. 2.Concentraciones de IL-6, sIL-6R y PCR en los momentos especificados. 3.Incidencia e intensidad de los acontecimientos adversos, con determinación de la intensidad conforme al modelo de clasificación de los criterios terminológicos comunes para acontecimientos adversos del National Cancer Institute, versión 5.0. 4.Incidencia de acontecimientos adversos graves 5.Variación de las constantes vitales respecto al momento basal. 6.Variación de los resultados analíticos de interés con respecto al momento basal. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to Day 28 2. Up to Day 60 3-4. Up to approximately Day 60 5-6. Baseline (Day 1) to Day 60 |
1. Hasta el día 28 2. Hasta el día 60 3-4. Hasta aproximadamente el día 60 5-6. Visita basal (día 1) al día 60 |
|
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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | 15 |
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 |
Italy |
Spain |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of this study is defined as the date of the last visit of the last participant in the study or the date at which the last data point required for statistical analysis or safety follow-up is received from the last participant, whichever occurs later. The end of the study is expected to occur approximately 60 days after the last participant is enrolled. In addition, the Sponsor may decide to terminate the study at any time. |
El final de este estudio se define como la fecha de la última visita del último participante en el estudio o la fecha en la que se recibe el último punto de datos requerido para el análisis estadístico o el seguimiento de seguridad del último participante, lo que ocurra más tarde. Se espera que el final del estudio ocurra aproximadamente 60 días después de que se inscriba al último participante. Además, el Promotor puede decidir finalizar el estudio en cualquier momento. |
|
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 | 14 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |