E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing multiple sclerosis |
esclerosis múltiple recurrente |
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E.1.1.1 | Medical condition in easily understood language |
Relapsing multiple sclerosis |
esclerosis múltiple recurrente |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 determine the long-term safety and tolerability of SAR442168 in RMS participants |
Determinar la seguridad y tolerabilidad a largo plazo de SAR442168 en participantes con EMR |
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy of SAR442168 on disease activity, assessed by clinical and imaging methods |
Evaluar la eficacia de SAR442168 en la actividad de la enfermedad a partir de los síntomas clínicos y de las pruebas de imagen |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participants must have completed treatment in the DRI15928 study - Female participants must continue to use a double contraception method including a highly effective method of birth control from inclusion and up to 2 months after the last study dose, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. Menopause is defined as being amenorrheic for ≥12 months with plasma follicle stimulating hormone (FSH) level >30 UI/L. - Male participants whose partners are of childbearing potential (including breastfeeding women), must accept to use, during sexual intercourse, a double contraceptive method according to the following algorithm: (condom) plus (intrauterine device or hormonal contraceptive) from inclusion up to 3 months after the last dose. - Male participants whose partners are pregnant must use, during sexual intercourse, a condom from inclusion up to 3 months after the last dose. - Male participants must have agreed not to donate sperm from the inclusion up to 3 months after the last dose. - The participant must have given written informed consent prior to undertaking any study related procedure. |
I 01. Los participantes deben haber completado el tratamiento del estudio DRI15928 antes de la selección. I 02. Las participantes de sexo femenino deben continuar utilizando un método anticonceptivo doble que incluya un método anticonceptivo de gran eficacia desde la inclusión y hasta 2 meses después de la última dosis de estudio, excepto en caso de que se hayan sometido a esterilización al menos 3 meses antes o de que sean posmenopáusicas. La menopausia se define como amenorrea durante más de 2 años con un nivel de FSH en plasma superior a 30 UI/l. I 03. Los participantes de sexo masculino que tengan parejas con capacidad de concebir (incluidas las mujeres en periodo de lactancia) deben aceptar el uso, durante sus relaciones sexuales, de un método anticonceptivo doble de conformidad con el siguiente algoritmo: (preservativo) más (dispositivo intrauterino o anticonceptivo hormonal) desde la inclusión hasta 3 meses después de la última dosis. I 04. Los participantes de sexo masculino cuyas parejas estén embarazadas deben utilizar, durante sus relaciones sexuales, un preservativo desde la inclusión hasta 3 meses después de la última dosis. I 05. Los participantes de sexo masculino deben haber aceptado no donar semen desde la inclusión hasta 3 meses después de la última dosis. I 06. El participante debe haber otorgado su consentimiento informado por escrito antes de someterse a cualquier procedimiento relacionado con el estudio. |
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E.4 | Principal exclusion criteria |
- The participant has a confirmed concomitant laboratory or ECG abnormality or medical condition deemed by the investigator incompatible with continuation of SAR442168 treatment. - The participant has received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) between the last DRI15928 visit and the first treatment visit in the LTS16004 study. - The participant has received a non-study MS disease modifying treatment between the last IMP treatment in Study DRI15928 and inclusion in Study LTS16004, which by judgement of the Investigator may add unjustified risk to switching back and continuing trreatment with SAR442168. - Washout periods after treatment with non-study DMTs should be respected except for interferons or glatiramer acetate treatment. - The participant is receiving strong inducers or inhibitors of CYP3A or CYP2C8 hepatic enzymes. Note: Such drugs need to be stopped at least 5 half-lives before study drug administration. - The participant is receiving anticoagulant/antiplatelet therapies, including: • Acetylsalicylic acid (aspirin) (if more than 81 mg/day) • Antiplatelet drugs (eg, clopidogrel) • Warfarin (vitamin K antagonist) • Heparin, including low molecular weight heparin (antithrombin agents) • Dabigatran (direct thrombin inhibitor) • Apixaban, edoxaban, rivaroxaban (direct factor Xa inhibitors) Note: All above drugs need to be stopped at least 5 half-lives before study drug administration except for aspirin, which needs to be stopped at least 8 days beforehand. - Prior/concurrent clinical study experienceThe participant is taking part in another interventional clinical trial of another drug substance. - Uncooperative behavior or any condition that could make the participant potentially non-adherent with the study procédures - The participant is pregnant or is a breastfeeding woman. |
E 01. El participante presenta una enfermedad o una anomalía de ECG o analítica concomitante confirmada que el investigador considere incompatible con la continuación del tratamiento con SAR442168. E 02. El participante ha recibido una vacuna elaborada con microbios vivos (atenuada) (incluidas, entre otras, la de la varicela-zóster, la antipoliomielítica oral y la antigripal intranasal) entre la última visita del estudio DRI15928 y la primera visita de tratamiento del estudio LTS16004. E 03. El participante ha recibido un tratamiento modificador de la enfermedad para la EM diferente al fármaco del estudio entre la última visita del estudio DRI15928 y su inclusión en el estudio LTS16004 que, a criterio del investigador, puede añadir un riesgo injustificado a volver a cambiar y continuar el tratamiento con SAR442168. - Deben respetarse los períodos de lavado después del tratamiento con DMT no estudiados, excepto los interferones o el tratamiento con acetato de glatiramer. - El participante está recibiendo inductores o inhibidores fuertes de las enzimas hepáticas CYP3A o CYP2C8. Nota: dichos medicamentos deben interrumpirse al menos 5 vidas medias antes de la administración del medicamento en estudio. - El participante está recibiendo terapias anticoagulantes / antiplaquetarias, que incluyen: Ácido acetilsalicílico (aspirina) (si es más de 81 mg / día) Fármacos antiplaquetarios (p. Ej., Clopidogrel) Warfarina (antagonista de la vitamina K) Heparina, incluida la heparina de bajo peso molecular (agentes antitrombina) Dabigatran (inhibidor directo de la trombina) Apixabán, edoxabán, rivaroxabán (inhibidores directos del factor Xa) Nota: todos los medicamentos anteriores deben interrumpirse al menos 5 vidas medias antes de la administración del medicamento en estudio, excepto la aspirina> 80 mg, que debe interrumpirse al menos 8 días antes. - Experiencia previa / concurrente en el estudio clínico. El participante participa en otro ensayo clínico de intervención de otra sustancia farmacéutica. - Comportamiento no cooperativo o cualquier condición que pueda hacer que el participante sea potencialmente no adherente con los procedimientos del estudio. - La participante está embarazada o es una mujer que está amamantando. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1 - Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) : Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) 2 - Number of Participants with Potentially Clinically Significant Abnormalities : Potentially clinically significant abnormalities (PCSAs) determined by laboratory tests, electrocardiogram (ECG), or vital signs during the study period. |
1. Número de pacientes con Acontecimientos adversos (AA), acontecimientos adversos graves (AAG) 2. Número de pacientes con posibles anomalías clínicamente significativas (potentially clinically significant abnormalities, PCSA) en las pruebas de laboratorio, electrocardiograma (ECG) o constantes vitales durante el periodo del estudio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1, 2 : Baseline to final follow-up visit ( Month 60 plus 8 weeks) |
1,2: Desde la basal hasta la visita de seguimiento final (Mes 60 más 8 semanas) |
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E.5.2 | Secondary end point(s) |
1 - Number of new gadolinium (Gd)-enhancing T1 hyperintense lesions : New gadolinium (Gd)-enhancing T1 hyperintense lesions determined by brain Magnetic Resonance Imaging (MRI) 2 - Number of new or enlarging T2 lesions : T2 lesions, a marker of inflammatory activity and brain tissue destruction in RMS will be evaluated by MRI 3 - Total number of Gd-enhancing T1-hyperintense lesions : Total number of Gd-enhancing T1-hyperintense lesions 4 - Number of participants wih relapse (Annualized Relapse rate) : Annualized Relapse rate is defined as the number of participants with relapse during the study period. 5 - Change in Expanded Disability Status Scale (EDSS) from baseline over time : Standard EDSS assessments of neurological symptoms in each of 7 functional domains (visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral and bowel/bladder) will be performed. Ambulation will also be scored as part of the evaluation. |
1 - Número de nuevas lesiones hiperintensas T1 que mejoran el gadolinio (Gd): Nuevas lesiones hiperintensas T1 que aumentan el gadolinio (Gd) determinada por imágenes de resonancia magnética (RMN) en el cerebro 2 - Número de lesiones T2 nuevas o que se están agrandando: las lesiones T2, un marcador de la actividad inflamatoria y la destrucción del tejido cerebral en EMR se evaluarán mediante RMN 3 - Número total de lesiones T1-hiperintensas que mejoran Gd: Número total de lesiones T1-hiperintensas que mejoran Gd 4 - Número de participantes con recaída (tasa de recaída anualizada): la tasa de recaída anualizada se define como el número de participantes con recaída durante el período de estudio. 5 - Cambio en la Escala de Estado de Discapacidad Expandida (EDSS) desde el inicio a lo largo del tiempo: evaluaciones EDSS estándar de los síntomas neurológicos en cada uno de los 7 dominios funcionales (visual, tronco cerebral, piramidal [motor], cerebeloso [coordinación], sensorial, cerebral e intestinal / vejiga ) será realizado. La ambulación también se calificará como parte de la evaluación. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2, 3, 5 : Baseline to final follow-up visit ( Month 60 plus 8 weeks) 4 : Baseline to Month 60 |
1, 2, 3, 5: Desde la basal hasta la visita de seguimiento final (mes 60 más 8 semanas) 4: desde la basal al mes 60 |
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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) | 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) | Yes |
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 | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Part A = randomized controlled, Part B = open-label |
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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 | Yes |
E.8.2.3.1 | Comparator description |
continued treatment with the respective SAR442168 dose administered |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Czech Republic |
Estonia |
France |
Netherlands |
Russian Federation |
Slovakia |
Spain |
Ukraine |
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 |
Última visita del último paciente |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 | 17 |