E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting multiple sclerosis (RRMS) |
Esclerosis múltiple recidivante-remitente (EMRR) |
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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 | 20.0 |
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 evaluate the efficacy of natalizumab extended interval dosing (EID) in subjects who have previously been treated with natalizumab standard interval dosing (SID) for at least 12 months, in relation to continued SID treatment. |
El objetivo principal del estudio es evaluar la eficacia del IAA de natalizumab en sujetos que hayan sido tratados previamente con un IEA de natalizumab durante al menos 12 meses, en relación con un tratamiento de IEA continuado. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate additional clinical and MRI based efficacy endpoints, and safety of EID in subjects who have previously been treated with natalizumab SID for at least 12 months, in relation to continued SID treatment. |
Evaluar otras medidas de la eficacia clínica basadas en recidivas con un IAA de natalizumab en sujetos que hayan sido tratados previamente con un IEA de natalizumab durante al menos 12 meses, en relación con la continuación del tratamiento con un IEA. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Ability of the participant to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations. • Diagnosis of relapsing remitting multiple sclerosis (RRMS) according to the McDonald criteria [Thompson 2018]. • Treatment with natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing for a minimum of 12 months prior to randomization. The participant must have received at least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months prior to randomization. • Expanded Disability Status Scale (EDSS) <=5.5 at screening. • No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator
NOTE: Other protocol-defined inclusion criteria may apply. |
• Capacidad del sujeto de comprender el propósito y los riesgos del estudio y proporcionar el consentimiento informado firmado y fechado así como la autorización para usar información médica de acuerdo con la normativa nacional y local sobre la privacidad de los sujetos. • Diagnóstico de EMRR según los criterios de McDonald [Thompson 2018]. • Tratamiento con natalizumab como monoterapia modificadora de la enfermedad para la EMRR y con una dosis coherente con la administración aprobada durante un mínimo de 12 meses antes de la aleatorización. El sujeto debe haber recibido un mínimo de 11 dosis de natalizumab en los 12 meses anteriores a la aleatorización y no haber omitido ninguna dosis en los 3 meses anteriores a la aleatorización. • EDSS ≤5,5 en la selección. • Sin recidivas en los 12 últimos meses anteriores a la aleatorización, según lo determinado por el investigador que realiza la inscripción.
NOTA: Otros criterios de inclusion definidos en el protocolo podrian aplicar |
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E.4 | Principal exclusion criteria |
• Primary and secondary progressive multiple sclerosis (MS). • MRI positive for Gd-enhancing lesions at screening. • Participants for whom MRI is contraindicated (e.g., have a contraindicated pacemaker or other contraindicated implanted metal device, have suffered, or are at risk for, side effects from Gd, or have claustrophobia that cannot be medically managed). • History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study, in the opinion of the Investigator. • Presence of anti-natalizumab antibodies at screening.
NOTE: Other protocol-defined exclusion criteria may apply. |
• EM progresiva primaria y secundaria. • RM positiva para lesiones potenciadas con Gd en la selección. • Los sujetos para los que la RM está contraindicada (p. ej., llevan un marcapasos contraindicado u otros implantes metálicos contraindicados, han sufrido o presentan riesgo de sufrir efectos secundarios con Gd o padecen claustrofobia que no se puede controlar médicamente). • Antecedentes de cualquier enfermedad cardíaca, endocrinológica, hematológica, hepática, inmunitaria, metabólica (incluido la diabetes), urológica, pulmonar, neurológica (excepto la EMRR), dermatológica, psiquiátrica, renal u otra enfermedad importante clínicamente significativa (según lo determinado por el investigador) que impida participar en un estudio clínico, en opinión del investigador. • Presencia de anticuerpos contra natalizumab en la selección.
NOTA: Otros criterios de inclusion definidos en el protocolo podrian aplicar |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 48 |
Número de lesiones hiperintensas en T2 nuevas o que hayan aumentado de tamaño en la semana 48. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
•Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC) •Number of new Gadolinium (Gd) Enhancing and new T1 Hypointense Lesions at Weeks 24, 48 and 72 •Annualized Relapse Rate at Weeks 48 and 72 •Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 72 •Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
o Tiempo hasta la primera recidiva (las recidivas serán adjudicadas por un comité independiente de evaluación neurológica) o Número de nuevas lesiones hipointensas en T1 y de nuevas lesiones potenciadas con gadolinio (Gd) en las semanas 24, 48 y 72 o Número de lesiones hiperintensas en T2 nuevas o que hayan aumentado en la semana 24 y la semana 72 o Evaluaciones de seguridad de los acontecimientos adversos y acontecimientos adversos graves |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Variable time frames throughout the study |
Marcos de tiempo variables a lo largo 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 | 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) | 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 | 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) | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Netherlands |
New Zealand |
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |