E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Sclerosis |
Esclerosis Múltiple |
|
E.1.1.1 | Medical condition in easily understood language |
Multiple Sclerosis |
Esclerosis Múltiple |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 |
To assess the effect of teriflunomide in comparison to placebo on disease activity measured by time to first clinical relapse after randomization in children and adolescents 10 to 17 years of age with relapsing forms of multiple sclerosis. |
Evaluar el efecto de teriflunomida en comparación con placebo sobre la actividad de la enfermedad medida a través del tiempo transcurrido hasta la primera recidiva clínica posterior a la aleatorización en niños y adolescentes de 10 a 17 años de edad con formas recurrentes de esclerosis múltiple. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of teriflunomide in comparison to placebo on disease activity/progression measured by brain MRI and on cognitive function. To evaluate the safety and tolerability of teriflunomide in comparison to placebo. To evaluate the pharmacokinetics (PK) of teriflunomide. |
- Evaluar el efecto de teriflunomida en comparación con placebo sobre la actividad/progresión de la enfermedad medidas mediante RMN del cerebro y sobre la función cognitiva. - Evaluar la seguridad y la tolerabilidad de teriflunomida en comparación con placebo. - Evaluar la farmacocinética (FC) de teriflunomida. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with relapsing multiple sclerosis (MS) based on McDonald criteria of 2010 and International Pediatric Multiple Sclerosis Study Group (IPMSG) criteria for pediatric MS: -at least one relapse in the 12 months preceding randomization, or -at least 2 relapses in the 24 months preceding randomization. - Equal or less than 17 years of age and equal or greater than 10 years of age at randomization. - Signed informed consent/assent obtained from patient and patient's legal representative. |
Pacientes con diagnóstico de EM recurrente basado en los criterios para la EM pediátrica de McDonald de 2010 y del Grupo de Estudio Internacional de la Esclerosis Múltiple Pediátrica y que reúnan estos requisitos: - al menos 1 recidiva en los 12 meses previos a la aleatorización; o - al menos 2 recidivas en los 24 meses previos a la aleatorización. ?17 años y ?10 años en el momento de la aleatorización. Obtención del consentimiento informado firmado/asentimiento del paciente y de su representante legal (padres o tutores) según la normativa local. |
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E.4 | Principal exclusion criteria |
- Expanded disability status scale (EDSS) score greater than 5.5 at screening or randomization visit. - Relapse within 30 days prior to randomization. - Treated with cladribine or mitoxantrone within 2 years preceding randomization. - Treated with glatiramer acetate, interferons, natalizumab, introvenous immunoglobulins or other immunosuppressant or immunomodulatory agents such as cyclophosphamide, azathioprine, cyclosporine, methotrexate, mycophenolate, dimetthyl fumrate, fingolimod less than 3 months or five half-lives prior to randomization, whichever is greater. - History of human immunodeficiency virus (HIV) infection. - Contraindication for magnetic resonance imaging (MRI). - Pregnant or breast-feeding females or those who plan to become pregnant during the study. - Female patients of child-bearing potential not using highly effective contraceptives or (double barrier) contraceptive method. |
Puntuación en la Escala ampliada del estado de discapacidad (Expanded Disability Status Scale, EDSS) >5,5 en las visitas de selección o de aleatorización. Recidiva en los 30 días anteriores a la aleatorización. Haber recibido tratamiento con cladribina o mitoxantrona en los 2 años previos a la aleatorización. Haber recibido tratamiento con acetato de glatirámero, interferones, natalizumab, inmunoglobulinas intravenosas u otros inmunosupresores o inmunomoduladores como ciclofosfamida, azatioprina, ciclosporina, metotrexato, micofenolato, dimetilfumarato o fingolimod menos de 3 meses o de 5 vidas medias antes de la aleatorización, el período más largo. Antecedentes de infección por VIH. Contraindicación para RMN. Mujeres embarazadas o que estén en período de lactancia o que tengan previsto quedarse embarazadas durante el estudio. Mujeres en edad fértil que no utilicen anticonceptivos o un método anticonceptivo (doble barrera) altamente eficaz. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first clinical relapse after randomization |
Tiempo transcurrido hasta la primera recidiva clínica después de la aleatorización. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 96 weeks |
Hasta 96 semanas |
|
E.5.2 | Secondary end point(s) |
1 - Proportion of relapse free patients 2 - Number of of new/newly enlarged T2 lesions 3 - Number of T1 Gd-enhancing T1 lesions 4 - Change in volume of T2 lesions 5 - Change in volume of T1 hypointense lesions 6 - Number of new T1 hypointense lesions 7 - Change in brain atrophy 8 - Change in performance on symbol digit modalities test (SDMT) and Cognitive Battery Test 9 - Overview of safety including adverse events (AEs) based on AE reporting, physical examinations, vital signs, clinical laboratories, suspected neuropathy, electrocardiography (ECG), suspected infection 10 - Teriflunomide pharmacokinetics (PK) to allow the dose adjustment to the 14 mg adult equivalent dose for the rest of the study |
1 - Proporción de pacientes sin recidivas. 2 - Número de lesiones en T2 nuevas o aumentadas 3 - Número de lesiones en T1 realzadas con Gd 4 - Cambio en el volumen de las lesiones en T2 5 - Cambio en el volumen de las lesiones hipointensas en T1 6 - Número de lesiones nuevas hipointensas en T1 7 - Atrofia cerebral 8 - Resultado de cognición medido a través de la Prueba de las Modalidades de Símbolos y Dígitos (Symbol Digit Modalities Test, SDMT) y una Prueba de la Batería Cognitiva cuando esté disponible. 9 - Acontecimientos adversos (AA), exploraciones físicas, signos vitales, pruebas de laboratorio, neuropatías, ECG, sospecha de infección 10 - FC de teriflunomida. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 and 9 : Over 96 weeks 2, 3, 4, 5, 6 and 7 : At randomization, at 24, 48 and 96 weeks 8 : At randomization, then every 24 weeks (SDMT only) and at 96 weeks 10 : A total of 3 PK samples (blood samples) will be collected during the beginning of study, i.e., the 4-week PK run-in period (weeks 2, 3 and 4); patients entering the open label teriflunomide arm will re-do PK run-in (3 blood samples) |
1 y 9: Hasta 96 semanas 2,3, 4, 5, 6 y 7: A la aleatorización, a la semana 24, 48 y 96 semanas 8: A la aleatorización, y cada 24 semanas (SDMT sólo) y a las 96 semanas. 10: Un total de 3 muestras de FC (muestras de sangre) serán recogidas durante el inicio del estudio. |
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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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Option to go in an open label teriflunomide arm for patients having a relapse after PK run-in phase |
|
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Canada |
China |
Australia |
Lebanon |
Israel |
Russian Federation |
Turkey |
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 |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 3 |