E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing Multiple Sclerosis |
Esclerosis múltiple recurrente |
|
E.1.1.1 | Medical condition in easily understood language |
Relapsing Multiple Sclerosis |
Esclerosis múltiple recurrente |
|
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 efficacy of SAR442168 in reducing the number of new brain lesions reported in Magnetic Resonance Imaging (MRI) |
Determinar la relación dosis-respuesta de SAR442168 en la reducción del número de lesiones cerebrales activas nuevas |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of SAR442168 on clinical symptoms and imaging measures - To evaluate the safety and tolerability of SAR442168 |
- Evaluar la eficacia de SAR442168 en la actividad de la enfermedad a partir de los síntomas clínicos y de los resultados de las pruebas de imagen - Evaluar la seguridad y la tolerabilidad de SAR442168 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent. - Participant must have been diagnosed with relapsing multiple sclerosis (RMS) according to the 2017 revision of the McDonald diagnostic criteria. - Participant must have at least 1 documented relapse within the previous year, ≥2 documented relapses within the previous 2 years, or ≥1 active Gadolinium (Gd)-enhancing brain lesion on an magnetic resonance imaging (MRI) scan in the past 6 months and prior to screening. - A female participant must use a double contraception method including a highly effective method of birth control, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. - 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. - Participant must have given written informed consent prior to undertaking any study-related procedure. |
- El participante debe tener entre 18 y 55 años de edad, inclusive, en el momento de firmar el consentimiento informado. - El participante debe haber sido diagnosticado con esclerosis múltiple (RMS) recurrente de acuerdo con la revisión de 2017 de los criterios diagnósticos de McDonald. - El participante debe tener al menos 1 recaída documentada dentro del año anterior, 2 ó más recaídas documentadas dentro de los 2 años anteriores, o 1 ó más lesiones cerebrales activas realzadas con gadolinio (Gd) en una imagen de Resonancia Magnética (MRI)en los últimos 6 meses y antes de la selección. - Una participante femenina debe usar un método anticonceptivo doble que incluya un método anticonceptivo altamente eficaz, excepto si se ha sometido a una esterilización al menos 3 meses antes o es posmenopáusica. - Los participantes masculinos, cuyas parejas son potencialmente fértiles (incluidas las mujeres que amamantan), deben aceptar utilizar, durante las relaciones sexuales, un método anticonceptivo doble de acuerdo con el siguiente algoritmo: (condón) más (dispositivo intrauterino o anticonceptivo hormonal) desde la inclusión hasta 3 meses después de la última dosis. - Los participantes masculinos cuyas parejas están embarazadas deben usar, durante las relaciones sexuales, un condón desde su inclusión hasta 3 meses después de la última dosis. - Los participantes masculinos deben haber acordado no donar esperma desde la inclusión hasta 3 meses después de la última dosis. - El participante debe haber dado su consentimiento informado por escrito antes de realizar cualquier procedimiento relacionado con el estudio. |
|
E.4 | Principal exclusion criteria |
- The participant has been diagnosed with primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with non relapsing secondary progressive multiple sclerosis (SPMS). - Requirement for concomitant treatment that could bias the primary evaluation. - Contraindication for MRI. - Contraindications to use MRI Gd contrast-enhancing preparations. - History of infection with the human immunodeficiency virus (HIV). - History of active or latent tuberculosis. - Any other active infections that would adversely affect participation or investigational medicinal product (IMP) administration in this study, as judged by the Investigator. - Presence of any screening laboratory or ECG values outside normal limits that are considered in the Investigator’s judgment to be clinically significant. - Presence of liver injury. - At screening, the participant is positive for hepatitis B surface antigen and/or hepatitis B core antibody and/or is positive for hepatitis C antibody. - Bleeding disorder or known platelet dysfunction at any time prior to screening visit. - Participant has received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) within 2 months before first treatment visit. - Participant is receiving strong inducers or inhibitors of CYP3A or CYP2C8 hepatic enzymes. - Participant is receiving anticoagulant/antiplatelet therapies. - Participant has taken other investigational drugs within 3 months or 5 half lives, whichever is longer, before screening visit. - Participant has an Expanded Disability Status Scale (EDSS) score >5.5 at screening visit. - Participant has had a relapse in the 30 days prior to randomization. - Participant is pregnant or a breastfeeding woman. - History or presence of significant other concomitant illness. - The participant has received medications/treatments for MS within a specified time frame. |
- El participante ha sido diagnosticado con esclerosis múltiple progresiva primaria (PPMS) de acuerdo con la revisión de 2017 de los criterios de diagnóstico de McDonald o con esclerosis múltiple progresiva secundaria no recurrente (SPMS). - Cualquier tratamiento concomitante que podría sesgar la evaluación primaria. - Contraindicación para la resonancia magnética. - Contraindicaciones para el uso de preparaciones de contraste de MRI Gd. - Historial de infección con el virus de la inmunodeficiencia humana (VIH). - Antecedentes de tuberculosis activa o latente. - Cualquier otra infección activa que pudiera afectar de manera adversa la participación o la administración de medicamentos en investigación (IMP) en este estudio, a juicio del investigador. - Presencia de cualquier valor de laboratorio o de ECG fuera de los límites normales que se consideren clínicamente significativos. - Presencia de lesión hepática. - En la selección, el participante que es positivo para el antígeno de superficie de la hepatitis B y / o el anticuerpo del núcleo de la hepatitis B y / o es positivo para el anticuerpo de la hepatitis C. - Trastorno de sangrado o disfunción plaquetaria conocida en cualquier momento antes de la visita de selección. - El participante ha recibido cualquier vacuna viva (atenuada) (que incluye, entre otras, varicela zóster, polio oral y gripe nasal) dentro de los 2 meses anteriores a la primera visita de tratamiento. - El participante está recibiendo inductores o inhibidores fuertes de las enzimas hepáticas CYP3A o CYP2C8. - El participante está recibiendo terapias anticoagulantes / antiplaquetarias. - El participante ha tomado otros medicamentos en investigación dentro de los 3 meses o 5 vidas medias, lo que sea más largo, antes de la visita de selección. - El participante tiene una puntuación de Escala de estado de discapacidad expandida (EDSS) superior a 5.5 en la visita de selección. - El participante tuvo una recaída en los 30 días previos a la aleatorización. - La participante está embarazada o amamantando. - Historia o presencia de otras enfermedades concomitantes significativas. - El participante ha recibido medicamentos / tratamientos para la EM dentro de un período de tiempo especificado. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of new Gd-enhancing T1 hyperintense lesions : Number of new Gd-enhancing T1 hyperintense lesions at the end of 12 weeks of SAR442168 treatment as detected by brain MRI |
Número de nuevas lesiones hiperintensas en T1 realzadas con Gd después de 12 semanas de tratamiento con SAR442168 confirmadas mediante RMN cerebral |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 12 for Arms 1-4, Week 4 and Week 16 for Arms 5-8 |
Semana 12 para los brazos 1-4, semana 4 y semana 16 para los brazos 5-8 |
|
E.5.2 | Secondary end point(s) |
1 - Number of new or enlarging T2 lesions : Number of new or enlarging T2 lesions at the end of 12 weeks of SAR442168 treatment 2 - Total number of Gd-enhancing T1 hyperintense lesions : Total number of Gd-enhancing T1-hyperintense lesions at the end of 12 weeks of SAR442168 treatment 3 - Adverse events : Number (n) and percentage (%) of participants experiencing an adverse event (AE)/Serious Adverse Event (SAE) or potentially clinically significant abnormalities in laboratory tests, electrocardiogram (ECG), or vital signs |
1. Número de nuevas lesiones en T2 o que hayan aumentado de tamaño después de 12 semanas de tratamiento con SAR442168 2. Número de nuevas lesiones hiperintensas en T1 realzadas con Gd después de 12 semanas de tratamiento con SAR442168 3. Acontecimientos adversos: número (n) y porcentaje (%) de participantes que experimentaron un acontecimiento adverso (AA) / grave (AAG) o anomalías clínicamente significativas en las pruebas de laboratorio, electrocardiograma (ECG) o constantes vitales durante el periodo del estudio |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2 : Week 12 for Arms 1-4, Week 4 and Week 16 for Arms 5-8 3 : From baseline to the end of study (approximately 20 weeks) |
1, 2: Semana 12 para los Brazos 1-4, Semana 4 y Semana 16 para los Brazos 5-8 3: desde el inicio hasta el final del estudio (aproximadamente 20 semanas) |
|
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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 8 |
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 | 6 |
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 |
Norway |
Russian Federation |
Slovakia |
Spain |
Sweden |
Ukraine |
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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |