E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Polyarticular-course juvenile idiopathic arthritis (pcJIA) |
Artritis idiopática juvenil poliarticular (AIJP) |
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E.1.1.1 | Medical condition in easily understood language |
Children with pcJIA have arthritis that causes pain and swelling in the joints and which, if not treated, can lead to pronounced disability |
Los niños con AIJP tienen artritis que causa dolor e hinchazón en las articulaciones y si no es tratada, puede llevar a discapacidad pronunciada |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059176 |
E.1.2 | Term | Juvenile idiopathic arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
Primary Objective - To characterize the pharmacokinetics of subcutaneous tocilizumab (SC TCZ) in patients with pcJIA. |
Objetivo primario - Definir la farmacocinética de tocilizumab subcutáneo en pacientes con AIJp |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives - To evaluate the pharmacodynamics of SC TCZ in patients with pcJIA - To evaluate the safety of SC TCZ in patients with pcJIA
Exploratory Objective - To describe the efficacy of SC TCZ in patients with pcJIA |
Objetivos secundarios - Evaluar la farmacodinamia de TCZ SC en pacientes con AIJp - Evaluar la seguridad de TCZ SC en pacientes con AIJp
Objetivo exploratorio El objetivo exploratorio de este estudio es describir la eficacia de TCZ SC en pacientes con AIJp. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Children 1-17 years of age - Diagnosis of polyarticular-course juvenile idiopathic arthritis (RF+ or RF- polyarticular JIA or extended oligoarticular JIA) - Inadequate clinical response (in the opinion of the treating physician) to or inability to tolerate methotrexate - Concurrent treatment with DMARDs (including MTX), NSAIDs and oral corticosteroids is permitted - Discontinuation of any biologic agents (other than tocilizumab if the patient is receiving IV TCZ) for 2-20 weeks prior to baseline depending on biologic agent |
- Tener edades comprendidas entre 1 y 17 años - AIJp diagnosticada (AIJp FR-positivo, AIJp FR-negativo, AIJoe de curso poliarticular) - Haber presentado una respuesta clínica inadecuada (de acuerdo con la opinión del médico responsable del tratamiento) o intolerancia a un tratamiento previo con MTX - Estará permitido el tratamiento concomitante con FAMEs (incluyendo MTX), AINEs y corticosteroides orales - Suspensión de la administración de agentes biólógicos (otros diferentes a tocilizumab si el paciente esta recibiendo TCZ IV) de 2-20 semanas antes del inico dependiendo del agente biológico |
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E.4 | Principal exclusion criteria |
- Prior discontinuation of IV TCZ because of inadequate clinical response or safety events - Patients with poorly controlled disease (in the opinion of the treating physician) despite current treatment with IV TCZ - pcJIA that is well controlled by any treatment agent other than TCZ (JADAS-71 <3.8) - Patients who are wheelchair-bound or bedridden - Any other auto-immune, rheumatic disease, or overlapping syndrome other than the permitted pcJIA subsets |
- Suspensión de un tratamiento previo con TCZ IV debido a respuesta clínica inadecuada o problemas de seguridad - Enfermedad mal controlada (de acuerdo con la opinión del médico responsable del tratamiento) a pesar del tratamiento actual con TCZ IV - AIJp bien controlada con cualquier agente terapéutico distinto de TCZ (puntuación JADAS-71 < 3,8) - Pacientes en silla de ruedas o encamados - Presentar cualquier otra enfermedad autoinmune, reumática o síndrome de superposición distintos de los subgrupos de AIJp permitidos |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Serum TCZ concentration and population PK model-predicted PK exposures (AUC, Cmax, and Cmin) for the Q2W and Q3W dosing regimens at steady state |
- Concentración sérica de TCZ y exposiciones FC previstas basadas en un modelo FC poblacional (área bajo la curva de la concentración plasmática-tiempo [AUC], concentración máxima [Cmax] y mínima [Cmin]) de los regímenes de administración C2S y C3S en estado de equilibrio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Fixed timepoints during the first 14 weeks of the study |
Se realizarán evaluaciones durante las 14 primeras semanas del estudio |
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E.5.2 | Secondary end point(s) |
Secondary endpoints - Serum IL-6 and soluble IL-6R (sIL-6R) levels, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) - The incidence and severity of adverse events (including local injection-site reactions) and serious adverse events - The incidence and severity of adverse events of special interest - The incidence and severity of clinical laboratory abnormalities -The incidence of anti-TCZ antibodies
Explolatory endpoints - Juvenile Arthritis Disease Activity Score (JADAS)-71 - Inactive disease and clinical remission - Childhood Health Assessment Questionnaire (CHAQ) |
Variables secundarias - Concentraciones séricas de IL-6 y sIL-6R, PCR y velocidad de sedimentación globular (VSG) - Incidencia y severidad de AA (incluyendo reacciones locales en la zona de inyección) y AAG - Incidencia y severidad de los acontecimientos adversos de especial interés (AAEI) - Incidencia y severidad de las anomalías de laboratorio clínico - Incidencia de anticuerpos anti-TCZ
Variables de valoración exploratorias - Puntuación de la actividad de la enfermedad en artritis juvenil (JADAS)-71 - Enfermedad inactiva y remisión clínica - Cuestionario para la evaluación del estado de salud en la infancia (CHAQ) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints - Pharmacodynamic endpoints will be evaluated at fixed timepoints during the first 14 weeks of the study [Weeks 0-14] - Adverse events, adverse events of special interest and clinical laboratory abnormalities will be recorded for the entire duration of the study [Weeks 0-52] - The presence of anti-TCZ antibodies will be evaluated at baseline and at regular intervals with event-driven testing in cases of anaphylaxis, serious hypersensitivity events, or any hypersensitivity event (including non-serious events) leading to treatment withdrawal (at the time of the event and at least 6 weeks after the event)
Exploratory endpoints - All endpoints will be measured for the duration of the study [Weeks 0-52] |
Variables secundarias - Se realizarán evaluaciones FD para evaluar los regímenes de administración durante las 14 primeras semanas del estudio (0-14 semanas) - Acontecimientos adversos, efectos adversos de especial interés y las anomalías de laboratorio clínico serán registradas durante toda la duración del estudio (0-52 semanas) - La presencia de anticuerpos anti-TCZ serán evaluados al inicio y en intervalos regulares con pruebas de detección en caso de anafilaxis, reacciones de hipersensibilidad graves, o cualquier reacción de hipersensibilidad que llevan a la retirada del tratamiento (en el momento de la reacción o al menos 6 semanas después)
Variables de valoración exploratorias - Todas las variables se medirán durante toda la duración del estudio (0-52 semanas) |
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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) | 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 |
dose evaluation in pediatric patients (adaptive design) |
evaluación de la dosis en pacientes pediátricos (diseño adaptativo) |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
France |
Germany |
Italy |
Peru |
Poland |
Russian Federation |
Spain |
United Kingdom |
United States |
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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 the study will occur when the last patient completes the last scheduled visit of the study or if the Sponsor decides for whatever reason to discontinue the study. |
Se producirá el fin del estudio cuando el último paciente complete la última visita programada del estudio o si el promotor decide por cualquier razon interrumpir el estudio. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 7 |