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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
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 |
Demonstrate that ofatumumab 20 mg sc once every 4 (q4) weeks is superior to teriflunomide 14 mg po once daily in reducing the frequency of confirmed relapses as evaluated by the annualized relapse rate (ARR) in patients with relapsing MS. |
Demostrar que ofatumumab 20 mg s.c. una vez cada 4 (q4) semanas es superior a teriflunomida 14 mg p.o. una vez al día para reducir la frecuencia de los brotes confirmados evaluados mediante la tasa anualizada de brotes (TAB) en pacientes con EM que cursa con brotes. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives
To evaluate if ofatumumab is superior to teriflunomide on: 1. Time to disability worsening as measured by 3-month confirmed worsening (3mCDW) on EDSS 2. Number of T1 GdE lesions per MRI scan 3. Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate) 4. Time to disability worsening as measured by 6-month confirmed worsening (6mCDW) on EDSS 5. Rate of brain volume loss (BVL) based on assessments of percentage brain volume change from baseline 6. Time to disability improvement, as measured by 6-month confirmed improvement (6mCDI) on EDSS
See protocol for complete list of secondary objectives. |
Objetivos secundarios clave Los objetivos secundarios clave son evaluar si ofatumumab es superior a teriflunomida en: 1.El tiempo hasta progresión de la discapacidad medido por el empeoramiento confirmado a los 3 meses (ECD3m) con EDSS 2.Número de lesiones captantes de Gd en T1 medidas por RM 3.Número de lesiones nuevas o mayores en T2 medidas por RM por año (tasa anualizada de lesiones en T2) 4.El tiempo hasta progresión de la discapacidad medido por el empeoramiento confirmado a los 6 meses (ECD6m) con EDSS 5.Tasa de pérdida de volumen cerebral (PVC) en base a las evaluaciones del porcentaje de cambio en el volumen cerebral desde la visita basal 6.El tiempo hasta progresión de la discapacidad medido por el empeoramiento confirmado a los 6 meses (ECD6m) con EDSS Ver en el protocol la lista complete de objetivos secundarios. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male or female patients aged 18 to 55 years (inclusive) at screening •Diagnosis of MS according to the 2010 Revised McDonald criteria •Relapsing form of MS: relapsing-remitting course (RRMS), or secondary progressive course with disease activity (relapsing SPMS) •Disability status at Screening with an EDSS score of 0 to 5.5 (inclusive) •At least 1 documented relapse during the previous 1 year OR at least 2 documented relapses during the previous 2 years OR a positive GdE MRI scan during the year prior to randomization and including screening. •Neurologically stable within 1 month prior to randomization
Please see protocol for complete detailed list of inclusion criteria |
- Pacientes hombres o mujeres de 18 a 55 años de edad (ambas edades inclusive) en la Selección - Diagnóstico de EM de acuerdo con los criterios revisados de McDonald 2010 - EM que cursa con brotes: curso remitente recurrente (EMRR), o curso secundario progresivo (EMSP) con actividad de la enfermedad - Estado de discapacidad en la Selección con una puntuación EDSS de 0 a 5,5 (ambas inclusive) - Documentación de al menos: 1 brote durante el último año O 2 brotes durante los 2 años anteriores antes de la Selección O una RM con captación de Gd durante el año previo a la aleatorización e incluyendo la selección. - Neurológicamente estable dentro del 1 mes previo a la aleatorización
Por favor, ver en el protocol el listado completo con los criterios de inclusión |
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E.4 | Principal exclusion criteria |
•Patients with primary progressive MS or SPMS without disease activity •Disease duration of more than 10 years in patients with EDSS score of 2 or less •Pregnant or nursing (lactating) women •Women of child-bearing potential not using highly effective contraception •Patients with an active chronic disease •Patients with active systemic infections, or history of or known presence of recurrent or chronic infection •Have received any live or live-attenuated vaccines within 2 months prior to randomization •Have been treated with medications as specified within the timeframes specified (e.g. ofatumumab, rituximab, ocrelizumab, alemtuzumab, natalizumab, cyclophosphamide, teriflunomide, etc) •Any other disease or condition which could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures.
Please see protocol for complete detailed list of exclusion criteria |
- Pacientes con EM primaria progresiva o EMSP sin actividad de la enfermedad - Duración de la enfermedad de más de 10 años en pacientes con una puntuación EDSS de 2 o menos - Mujeres embarazadas o en período de lactancia - Mujeres en edad fertil que no estén utilizando métodos altamente eficaces de anticoncepción - Pacientes con una enfermedad crónica active - Pacientes con infecciones sistémicas activas, o historia o presencia conocida de infecciones crónicas o recurrentes. - Haber recibido alguna vacuna viva o viva atenuada en los 2 meses previos a la aleatorización - Haber sido tratado con alguna de las medicaciones que se listan a continuación (e.j.: ofatumumab, rituximab, ocrelizumab, alemtuzumab, natalizumab, cyclophosphamide, teriflunomide, etc) - Cualquiera otra enfermedad o condición que pudiera interferir en la participacion en el estudio de acuerdo con el protocolo o con la posibilidad de los pacientes de cooperar y cumplir con los procedimientos del estudio. Por favor, ver en el protocol el listado completo con los criterios de exclusión |
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E.5 End points |
E.5.1 | Primary end point(s) |
Demonstrate that ofatumumab 20 mg sc once every 4 (q4) weeks is superior to teriflunomide 14 mg po once daily in reducing the frequency of confirmed relapses as evaluated by the annualized relapse rate (ARR) in patients with relapsing MS. |
Demostrar que ofatumumab 20 mg s.c. una vez cada 4 (q4) semanas es superior a teriflunomida 14 mg p.o. una vez al día para reducir la frecuencia de los brotes confirmados evaluados mediante la tasa anualizada de brotes (TAB) en pacientes con EM que cursa con brotes. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 30 months |
Máximo 30 meses |
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E.5.2 | Secondary end point(s) |
-Time to disability worsening as measured by 3-month confirmed worsening (3mCDW) on The Expanded Disability Status Scale (EDSS). -Time to disability worsening as measured by 6-month confirmed worsening (6mCDW) on EDSS. -Time to disability improvement as measured by 6-month confirmed improvement (6mCDI) on EDSS. -Number of T1 Gd-enhancing lesions per MRI scan. -Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate). -Rate of brain volume loss (BVL) based on assessments of percentage brain volume change from baseline. |
- El tiempo hasta progresión de la discapacidad medido por el empeoramiento confirmado a los 3 meses (ECD3m) con la escala ampliada del estado de discapacidad (EDSS) - El tiempo hasta progresión de la discapacidad medido por el empeoramiento confirmado a los 6 meses (ECD6m) con EDSS - El tiempo hasta la mejoría de la discapacidad medida por la mejoría confirmada a los 6 meses (MCD6m) con EDSS - Número de lesiones captantes de Gd en T1 medidas por RM - Número de lesiones nuevas o mayores en T2 medidas por RM por año (tasa anualizada de lesiones en T2) - Tasa de pérdida de volumen cerebral (PVC) en base a las evaluaciones del porcentaje de cambio en el volumen cerebral desde la visita basal |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 30 months |
Máximo 30 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 | 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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 116 |
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 |
Canada |
Chile |
India |
Israel |
Korea, Republic of |
Kuwait |
Mexico |
Russian Federation |
Saudi Arabia |
Switzerland |
Thailand |
Turkey |
United States |
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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
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LVLS |
Ultima visita del ultimo sujeto |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 9 |