E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-Remitting Multiple Sclerosis |
Esclerosis múltiple recidivante-remitente |
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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 | 17.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting 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 |
The primary objective of this study is to determine whether DMF taken over 12 months is effective in reducing MS related fatigue, as measured by mean changes in the Fatigue Scale for Motor and Cognitive Functions (FSMC), in subjects with RRMS. |
El objetivo principal del estudio es determinar si el tratamiento con DMF durante 12 meses disminuye eficazmente el cansancio asociado a la EM, determinado mediante la variación media en la Escala de cansancio para las funciones motoras y cognitivas (FSMC), en pacientes con EMRR. |
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E.2.2 | Secondary objectives of the trial |
To investigate changes from Baseline in FSMC and fatigue severity (Fatigue Severity Scale [FSS]) at 1, 3, 6, 9, and 12 months in subjects receiving DMF
To assess the impact of DMF on patient reported outcomes (PROs), including work productivity (Work Productivity and Activity Impairment-Multiple Sclerosis questionnaire [WPAI-MS]), health-related quality of life (Short Form Health Survey [SF-12] or the 15-dimensional health-related quality of life [15D HRQoL] questionnaire), depression (Beck Depression Inventory-Fast Screen [BDI-FS]), and sleepiness (Epworth Sleepiness Scale [ESS]) at 6 and 12 months in subjects receiving DMF
To examine whether an association exists between fatigue and baseline demographics (e.g., age and sex) and disease characteristics (e.g., disease duration, baseline disease activity, treatment history, expanded disability status scale [EDSS] score, and PROs)
To assess any changes in fatigue-related medication use |
Investigar la variación de la FSMC y de la intensidad del cansancio (Escala FSS) entre el momento basal y los meses 1, 3, 6, 9 y 12 de tratamiento con DMF. Evaluar el efecto del tratamiento con DMF sobre los resultados comunicados por los pacientes (RCP) acerca de la productividad laboral (Cuestionario WPAI-MS), la calidad de vida relacionada con la salud (Cuestionario SF-12 o Cuestionario 15D HRQoL), la depresión (Escala de depresión de Beck - evaluación rápida [BDI-FS]) y la somnolencia (Escala de somnolencia de Epworth [ESS]) a los 6 y 12 meses de tratamiento con DMF. Analizar si existe relación entre el cansancio, los datos demográficos (por ejemplo, sexo, edad) y las características clínicas basales (por ejemplo, duración de la enfermedad, actividad de la enfermedad en el momento basal, tratamientos previos, puntuación en la Escala ampliada del estado de discapacidad [EDSS] y RCP). Evaluar todos los cambios efectuados en la medicación para el cansancio. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Biomarker Sub-Study. Subjects who consent to participate will provide blood samples that will be used to identify or verify deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and serum markers associated with disease and response to DMF. |
Subestudio de análisis de biomarcadores. Los sujetos que acceden a participar proporcionarán muestras de sangre que se utilizarán para identificar o verificar en las muestras la presencia de ácido desoxirribonucleico (ADN), ácido ribonucleico (ARN), y los marcadores séricos de la enfermedad y su respuesta al DMF. |
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E.3 | Principal inclusion criteria |
Have the ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
Have a confirmed diagnosis of RRMS and satisfy the therapeutic indication as described in the local label.
Have a stable EDSS (as assessed by the Investigator) and have been on the same (type and dosage) standard of care first line treatment for at least 6 months.
If taking antidepressants, amphetamine, modafinil, or fampridine (Fampyra), subject must be assessed as having been clinically stable for at least 3 months prior to the Baseline Visit.
Age >= 18 years at the time of informed consent.
FSMC total score >= 43 (mild fatigue) at Baseline.
As perceived by the Investigator, have the ability to comply with all requirements of the study protocol.
Female subjects of childbearing potential who are not surgically sterile must practice effective contraception during their participation in the study and be willing and able to continue contraception for 12 weeks after their last dose of study treatment. |
Tener la capacidad de comprender el objetivo y los riesgos del estudio y de dar el consentimiento informado por escrito, firmando y fechando el documento correspondiente, así como de autorizar la utilización de información sanitaria confidencial conforme a la legislación nacional y local de confidencialidad de los datos del paciente.
Tener un diagnóstico confirmado de EMRR y cumplir la indicación terapéutica que se indica en la ficha técnica local.
Presentar una EMRR estable (conforme a lo determinado por el investigador) y haber recibido el mismo tratamiento de primera línea de referencia (tipo y dosis) durante los últimos seis meses.
En caso de recibir tratamiento con antidepresivos, anfetamina, modafinilo o fampridina (Fampyra), el paciente deberá haber permanecido clínicamente estable desde al menos tres meses antes de la visita basal.
Edad >= 18 años en el momento del consentimiento informado.
Puntuación total en la FSMC >= 43 (cansancio leve) en el momento basal.
Ser capaz, en opinión del investigador, de cumplir todos los requisitos del protocolo del estudio.
Las pacientes en edad fértil que no se hayan sometido a esterilización quirúrgica deberán utilizar métodos anticonceptivos eficaces durante su participación en el estudio y estar dispuestas a mantenerlos, y ser capaces de hacerlo, hasta 12 semanas después de la última dosis de tratamiento del estudio. |
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E.4 | Principal exclusion criteria |
Diagnosis of major depression, as identified by the Investigator.
Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS.
History of malignancy (except for basal cell carcinoma that had been completely excised prior to study entry), severe allergic or anaphylactic reactions or known drug hypersensitivity, abnormal laboratory results indicative of any significant disease, and/or a major disease that would preclude participation in a clinical trial.
History of a relapse within 90 days prior to study enrollment or showing transient symptoms derived from a previous relapse, irrespective of time of symptom onset.
Treatment of MS relapse within 90 days prior to study enrollment.
History of a positive test result for human immunodeficiency virus, hepatitis C virus antibody, or hepatitis B virus (defined as positive for hepatitis B surface antigen or hepatitis B core antibody.
Female subjects who are pregnant or planning to become pregnant during the study period, or who are currently breastfeeding.
Impaired hepatic or renal function, as perceived by the Investigator.
Any prior treatment with DMF (or other fumarate derivative), total lymphoid irradiation, cladribine, fingolimod, T cell or T-cell receptor vaccination, or any therapeutic monoclonal antibody.
Treatment within 1 year prior to study enrollment with mitoxantrone or cyclophosphamide.
Treatment within 6 months prior to study enrollment with cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, intravenous immunoglobulin, plasmapheresis, cytapheresis, or another investigational drug or approved therapy for investigational use.
Current enrollment in any other clinical studies.
Known to suffer from narcolepsy or another significant sleep disorder.
Comorbidity that may have an impact on fatigue.
Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment. |
Diagnóstico de depresión mayor identificado por el investigador.
Diagnóstico de EM progresiva primaria, progresiva secundaria o progresiva recidivante.
Antecedentes de neoplasia maligna (excepto el carcinoma basocelular extirpado por completo antes de la inclusión en el estudio), reacciones alérgicas graves o anafilácticas o hipersensibilidad a fármacos, anomalías analíticas indicativas de una enfermedad importante o enfermedad importante que impida la participación en un ensayo clínico.
Antecedentes de recidiva en los 90 días precedentes a la inclusión en el estudio o presencia de síntomas transitorios debidos a una recidiva previa, con independencia del momento en que apareció el síntoma.
Haber recibido tratamiento para una recidiva de la EM en los 90 días precedentes a la inclusión en el estudio.
Antecedentes de resultado positivo en la prueba del virus de la inmunodeficiencia humana, del anticuerpo del virus de la hepatitis C o del virus de la hepatitis B (definida como positividad para el antígeno de superficie o para el anticuerpo nuclear del virus de la hepatitis B).
Mujeres embarazadas o que tengan previsto quedarse embarazadas durante el estudio, o que estén en período de lactancia.
Trastorno de la función hepática o renal, a criterio del investigador.
Antecedentes de tratamiento con DMF (u otro derivado del fumarato), irradiación linfática total, cladribina, fingolimod, vacunas de linfocitos T o de receptores de linfocitos T o cualquier anticuerpo monoclonal terapéutico.
Tratamiento con mitoxantrona o ciclofosfamida durante el último año antes de la inclusión en el estudio.
Tratamiento con ciclosporina, azatioprina, metotrexato, micofenotalo mofetilo, inmunoglobulinas intravenosas, plasmaféresis, citaféresis, otro fármaco experimental u otro tratamiento aprobado para uso experimental en los seis meses previos a la inclusión en el estudio.
Participación actual en otros estudios clínicos.
Narcolepsia o cualquier otro trastorno importante del sueño.
Enfermedades concomitantes que afecten al cansancio.
Otro motivo no especificado que, en opinión del investigador o de Biogen Idec, impida la inclusión del paciente. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from Baseline in MS-related fatigue (FSMC) at 12 months in subjects receiving DMF. |
Variación media del cansancio asociado a la EM (FSMC) entre el momento basal y el mes 12 de tratamiento con DMF. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Mean change from Baseline in fatigue (FSMC and FSS) at 1, 3, 6, 9, and 12 months in subjects receiving DMF
Mean change from Baseline in work productivity, quality of life, depression, and sleepiness at 6 and 12 months in subjects receiving DMF
Change in MS-related fatigue (FSMC) status (improved [> 4.5 increase], stable [within ±4.5], and worsened [> 4.5 decrease])
Correlation of fatigue with baseline demographics and disease characteristics
Proportion of subjects with reduced dose or discontinuation of fatigue related medications at 6 and 12 months |
Variación media del cansancio (FSMC y FSS) entre el momento basal y los meses 1, 3, 6, 9 y 12 de tratamiento con DMF.
Variación media de la productividad laboral, la calidad de vida, la depresión y la somnolencia entre el momento basal y los meses 6 y 12 de tratamiento con DMF.
Variación del estado de cansancio asociado a la EM (FSMC) (mejoría [aumento > 4,5], estabilización [variación de ± 4,5] o empeoramiento [disminución > 4,5]).
Correlación entre el cansancio y las características demográficas y clínicas basales.
Porcentaje de pacientes a los que se ha reducido o retirado la medicación para el cansancio a los 6 y 12 meses. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Mean change from Baseline in fatigue (FSMC and FSS) at 1, 3, 6, 9, and 12 months in subjects receiving DMF
Mean change from Baseline in work productivity, quality of life, depression, and sleepiness at 6 and 12 months in subjects receiving DMF
Change in MS-related fatigue (FSMC) status (improved [> 4.5 increase], stable [within ±4.5], and worsened [> 4.5 decrease])
Correlation of fatigue with baseline demographics and disease characteristics
Proportion of subjects with reduced dose or discontinuation of fatigue related medications at 6 and 12 months |
Variación media del cansancio (FSMC y FSS) entre el momento basal y los meses 1, 3, 6, 9 y 12 de tratamiento con DMF.
Variación media de la productividad laboral, la calidad de vida, la depresión y la somnolencia entre el momento basal y los meses 6 y 12 de tratamiento con DMF.
Variación del estado de cansancio asociado a la EM (FSMC) (mejoría [aumento > 4,5], estabilización [variación de ± 4,5] o empeoramiento [disminución > 4,5]).
Correlación entre el cansancio y las características demográficas y clínicas basales.
Porcentaje de pacientes a los que se ha reducido o retirado la medicación para el cansancio a los 6 y 12 meses. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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LVLS: The end of study is last subject, last visit for final collection of data for the primary outcome. |
La última visita del último paciente: El fin del estudio es el úlltimo paciente, la última visita de la última recogida de datos para el resultado primario. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |