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    Summary
    EudraCT Number:2016-001448-21
    Sponsor's Protocol Code Number:MS200527-0086
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-10-26
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2016-001448-21
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 with a Parallel, Open-Label, Active Control Group (Tecfidera), in Patients with Relapsing Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity.
    Estudio en fase II aleatorizado, doble ciego y controlado con placebo sobre M2951 con un grupo de control activo, paralelo y abierto (Tecfidera) en pacientes con esclerosis múltiple recidivante para evaluar la eficacia, seguridad, tolerabilidad, farmacocinética y actividad biológica
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Efficacy and Safety of M2951 in Relapsing Multiple Sclerosis
    Estudio de la eficacia y seguridad de M2951 en la esclerosis múltiple recidivante
    A.4.1Sponsor's protocol code numberMS200527-0086
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck KGaA
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck KGaA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck KGaA
    B.5.2Functional name of contact pointCommunication Center Merck KGaA
    B.5.3 Address:
    B.5.3.1Street AddressFrankfurter Strasse 250
    B.5.3.2Town/ cityDarmstadt
    B.5.3.3Post code64293
    B.5.3.4CountryGermany
    B.5.4Telephone number+0034900810844
    B.5.6E-mailservice@merckgroup.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameM2951
    D.3.2Product code M2951
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNM2951
    D.3.9.2Current sponsor codeM2951
    D.3.9.3Other descriptive nameM2951
    D.3.9.4EV Substance CodeSUB180032
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tecfidera
    D.2.1.1.2Name of the Marketing Authorisation holderBiogen Idec Ltd
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTecfidera
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTecfidera
    D.3.9.1CAS number 624-49-7
    D.3.9.2Current sponsor codeDIMETHYL FUMARATE
    D.3.9.3Other descriptive nameDIMETHYL FUMARATE
    D.3.9.4EV Substance CodeSUB13608MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tecfidera
    D.2.1.1.2Name of the Marketing Authorisation holderBiogen Idec Ltd
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTecfidera
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTecfidera
    D.3.9.1CAS number 624-49-7
    D.3.9.3Other descriptive nameDIMETHYL FUMARATE
    D.3.9.4EV Substance CodeSUB13608MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number240
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsing Multiple Sclerosis
    Esclerosis múltiple recidivante
    E.1.1.1Medical condition in easily understood language
    Relapsing Multiple Sclerosis
    Esclerosis múltiple recidivante
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10028245
    E.1.2Term Multiple sclerosis
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10048393
    E.1.2Term Multiple sclerosis relapse
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to evaluate the efficacy and dose-response of M2951 on the number of gadolinium-positive (Gd+) T1 MRI lesions versus placebo after 24 weeks of treatment.
    El objetivo principal es evaluar la eficacia y la respuesta a la dosis de M2951 en la serie de lesiones observadas mediante resonancia magnética (RM) en T1 positivas para gadolinio (Gd+) en comparación con placebo tras 24 semanas de tratamiento.
    E.2.2Secondary objectives of the trial
    The key secondary objectives are as follows:
    - To evaluate the efficacy and dose-response of M2951 on clinical endpoints over 24 weeks versus placebo
    - To evaluate the safety of M2951

    Additional secondary objectives are as follows:
    - To evaluate the efficacy of M2951 on additional MRI parameters over 24 weeks versus placebo
    - To evaluate the efficacy of M2951 on clinical and MRI endpoints from Weeks 24 to 48
    - To evaluate the efficacy of Tecfidera on clinical and MRI endpoints over 24 weeks
    - To evaluate the efficacy of Tecfidera on clinical and MRI endpoints from Weeks 24 to 48
    - To evaluate the safety of Tecfidera
    Los objetivos secundarios principales son los siguientes:
    - Evaluar la eficacia y la respuesta a la dosis de M2951 en los criterios de valoración clínicos durante 24 semanas en comparación con placebo.
    - Evaluar la seguridad de M2951.

    El resto de objetivos secundarios son los siguientes:
    - Evaluar la eficacia de M2951 en parámetros de RM adicionales durante 24 semanas en comparación con placebo.
    • Evaluar la eficacia de M2951 en los criterios de valoración clínicos y de RM desde la semana 24 a la semana 48.
    • Evaluar la eficacia de Tecfidera en los criterios de valoración clínicos y de RM durante 24 semanas.
    • Evaluar la eficacia de Tecfidera en los criterios de valoración clínicos y de RM desde la semana 24 a la semana 48.
    • Evaluar la seguridad de Tecfidera.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Pharmacodynamics Bruton’s tyrosine kinase (BTK) occupancy (version and date as per current protocol).

    Bruton’s tyrosine kinase (BTK) occupancy samples will be taken from a subset of approximately 30 evaluable subjects treated with M2951 or placebo from selected sites capable of providing samples.

    Objective: To determine the Change from Baseline in percent BTK occupancy to predose on Days 28, 84 and 168 and 2 hours postdose on Days 1, 28, 84 and 168.
    farmacodinámica de la ocupación de la tirosina quinasa de Bruton (BTK)(versión y la fecha según el protocolo actual).

    Muestras de ocupación de tirosina quinasaB de ruton (BTK) se tomará a partir de un subconjunto de aproximadamente 30 sujetos evaluables tratados con placebo o M2951 de los centros sitios seleccionados capaces de proporcionar muestras.

    Objetivo: Determinar el cambio desde el inicio en el por ciento de ocupación de BTK antes de la dosis en los días 28, 84 y 168 y 2 horas después de la dosis en los días 1, 28, 84 y 168.
    E.3Principal inclusion criteria
    1. Subjects with a diagnosis of relapsing multiple sclerosis (may include subjects with Secondary PMS [SPMS] with superimposed relapses provided they meet the other criteria) in accordance with revised McDonald criteria for MS and Lublin and Reingold
    2. Male or female aged 18 to 65 years
    3. One or more documented relapses within the 2 years before Screening with either: a) One relapse which occurred within the last year prior to randomization or b) the presence of at least 1 Gd+ T1 lesion within 6 months prior to randomization would make the patient eligible.
    4. Expanded Disability Status Scale score of 0 to 6 at Baseline
    5. Women of childbearing potential must use a supplementary barrier method together with a highly effective method of contraception for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP. Male subjects and their female partners must also use the above.
    6. Signed and dated informed consent (subject must be able to understand the informed consent) indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrolment and will comply with the requirements of the protocol.
    1. Los sujetos con un diagnóstico de la esclerosis múltiple recidivante (pueden incluir sujetos con síndrome premenstrual secundarios [EMSP] con recaídas superpuestas siempre que cumplan los demás criterios) de acuerdo con los criterios revisados ​​de McDonald para la EM y Lublin y Reingold
    2. Hombre o mujer de entre 18 a 65 años
    3. Una o más recaídas documentadas en los 2 años antes de la selección, ya sea con: a) Una recaída que se produjo en el último año antes de la aleatorización o b) la presencia de al menos 1 lesión en T1 con gandolinio dentro de los 6 meses anteriores a la aleatorización.
    4. El sujeto debe contar con puntuación en la EDSS de 0 a 6 en la línea basal
    5. Las mujeres en edad fértil deben utilizar un método de barrera complementario junto con un método anticonceptivo muy eficaz durante 4 semanas antes de la aleatorización, durante todo el ensayo, y durante 90 días después de la última dosis de IMP. Los sujetos masculinos y sus parejas femeninas deben utilizar también los métodos anteriores.
    6. Firmar y fechar el consentimiento informado (sujeto debe ser capaz de entender el consentimiento informado) que indica que el sujeto ha sido informado de todos los aspectos pertinentes del estudio antes de la aceptación y cumplirá con los requisitos del protocolo.
    E.4Principal exclusion criteria
    • Progressive MS
    • Disease duration > 15 years in subjects with EDSS of 2 or less
    • Use of the following, as determined in the protocol ; rituximab, ocrelizumab, mitoxantrone, or lymphocyte-depleting therapies, lymphocyte trafficking blockers (eg, natalizumab, fingolimod), intravenous (IV) immunoglobulins (Ig), plasmapheresis, immunosuppressive treatments, B-interferons or glatiramer acetate, Systemic glucocorticoids, teriflunomide, daclizumab
    • Exposure to Tecfidera within 6 months prior to randomization
    • Any allergy, contraindication, or inability to tolerate Tecfidera
    • Treatment with dalfampridine (fampridine, Ampyra) unless on a stable dose for ≥ 30 days prior to randomization
    • Inability to comply with MRI scanning
    • Immunologic disorder other than MS, with the exception of secondary well-controlled diabetes or thyroid disorder, or any other condition requiring oral, IV, intramuscular, or intra-articular corticosteroid therapy
    • Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
    • Severe drug allergy or history of anaphylaxis, or allergy to the IMP or any of its incipients
    • Active, clinically significant viral, bacterial, or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of Screening, or completion of oral anti-infectives within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary.
    • History of or positive testing for human immunodeficiency virus (HIV), hepatitis C (HCV) antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg) (+) and/or hepatitis B core total, and/or IgM antibody (+) at Screening.
    • The subject: • Has a history of or current diagnosis of active tuberculosis (TB) or • Is currently undergoing treatment for latent TB infection (LTBI) or • Has an untreated LTBI or • Has a positive QuantiFERON®-TB test at Screening.
    • Indeterminate QuantiFERON®
    • Subjects with current household contacts with active TB will also be excluded
    • History of splenectomy or any major surgery within 2 months prior to Screening
    • History of myocardial infarction or cerebrovascular event as per the protocol
    • History of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS)
    • An episode of major depression within the last 6 months prior to Screening
    • On anticoagulation, fish oil supplements, or antiplatelet therapy other than daily aspirin for cardioprotection and treatment of Tecfidera induced flushing
    • History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin
    • Breastfeeding/lactating or pregnant women
    • Participation in any investigational drug trial within 1 month or 5 half-lives of the investigational drug, whichever is longest, prior to Screening
    • Subjects currently receiving (or unable to stop using prior to receiving the first dose of IMP) medications or herbal supplements known to be potent inhibitors of cytochrome P450 3A (CYP3A)
    • History of or current alcohol or substance abuse
    • Clinically significant abnormality on electrocardiogram or screening chest X-ray
    • Clinically significant laboratory abnormality
    • EM progresiva
    • duración de la enfermedad> 15 años en sujetos con EDSS de 2 o menos
    • Uso de los siguientes, según lo determinado en el protocolo; rituximab, ocrelizumab, mitoxantrona, o terapias de linfocitos de ozono, los bloqueadores de tráfico de linfocitos (por ejemplo, el natalizumab, fingolimod), intravenosa (iv) las inmunoglobulinas (Ig), plasmaféresis, tratamientos inmunosupresores, B-interferones o acetato de glatiramer, glucocorticoides sistémicos, teriflunomida, daclizumab
    • La exposición a Tecfidera en los 6 meses anteriores a la aleatorización
    • Cualquier alergia, contraindicación, o la incapacidad de tolerar Tecfidera
    • El tratamiento con dalfampridina (Fampridine, Ampyra) a menos que en una dosis estable durante ≥ 30 días antes de la aleatorización
    • Incapacidad para cumplir con la RM
    • trastorno inmunológico que no sea MS, con la excepción del trastorno de la diabetes o la tiroides bien controlado secundaria, o cualquier otra condición que requiera IV, intramuscular, o tratamiento con corticosteroides orales, intraarticular
    • La vacunación con la vacuna de virus vivo o viva atenuada dentro de 1 mes antes de la selección
    • Alergia grave de drogas o antecedentes de anafilaxia, o alergia a la PMI o cualquiera de sus incipientes
    • La infección activa, clínicamente significativa viral, bacteriana o micótica, o cualquier episodio de infección que requiere hospitalización o tratamiento con parenterales antiinfecciosos en el plazo de 4 semanas de seleccion, o la terminación de antiinfecciosos orales dentro de 2 semanas antes o durante el ensayo, o antecedentes de infecciones recurrentes (es decir, 3 o más del mismo tipo de infección en un período de 12 meses). La candidiasis vaginal, onicomicosis, y el virus del herpes simple genital u oral considerados por el investigador como suficientemente controlados no sería excluyente.
    • Historial de/o las pruebas positivas para el virus de la inmunodeficiencia humana (VIH), la hepatitis C (VHC) anticuerpos y / o reacción en cadena de la polimerasa, antígeno de superficie de la hepatitis B (HBsAg) (+) y / o hepatitis B total del núcleo, anticuerpos y / o IgM (+) en la selección.
    • El sujeto: • Tiene antecedentes o diagnóstico actual de la tuberculosis (TB) activa o • se encuentra actualmente en tratamiento para la infección tuberculosa latente (ITL) o • Tiene una infección latente no tratada o • Tiene una prueba de QuantiFERON-TB positiva en la selección.
    • Indeterminado QuantiFERON®
    • También deben excluirse los sujetos con datos actuales de TB activa
    • Historia de esplenectomía o cualquier cirugía mayor dentro de los 2 meses anteriores a la selección
    • Antecedentes de infarto de miocardio o accidente cerebrovascular según el protocolo
    • Historial de intentos de suicidio en los 6 meses anteriores a la selección o una respuesta positiva a los artículos 4 o 5 del Columbia-suicidio Gravedad de la Escala (C-SSRS)
    • Episodio de depresión mayor en los últimos 6 meses anteriores a la selección
    • En la anticoagulación, los suplementos de aceite de pescado, o la terapia antiplaquetaria que no sea una aspirina diaria por la cardioprotección y el tratamiento de lavado Tecfidera inducida
    • Antecedentes de cáncer, excepto células basales tratado adecuadamente o carcinoma de células escamosas de la piel
    • La lactancia materna/lactantes o mujeres embarazadas
    • La participación en cualquier ensayo clinico dentro de 1 mes o 5 vidas medias del fármaco en investigación, el que sea más largo, antes de la selección
    • Los sujetos que reciben actualmente (o que no pueden dejar de usar antes de recibir la primera dosis de IMP) medicamentos o suplementos herbales conocidos por ser potentes inhibidores del citocromo P450 3A (CYP3A)
    • Historial de abuso de determinadas sustancias o alcohol
    • anormalidad clínicamente significativa en el electrocardiograma o prueba de la radiografía de tórax
    • anormalidades de laboratorio clínicamente significativas
    E.5 End points
    E.5.1Primary end point(s)
    Total number of gadolinium-enhancing T1 lesions at Weeks 12, 16, 20, and 24
    Número total de lesiones T1 realizadas con gadolinio en las semanas 12, 16, 20 y 24
    E.5.1.1Timepoint(s) of evaluation of this end point
    Weeks 12, 16, 20 and 24
    Semanas 12, 16, 20 y 24
    E.5.2Secondary end point(s)
    Key secondary endpoints to evaluate the efficacy and safety of M2951 compared to placebo:
    • Annualized relapse rate (ARR), based on protocol-defined qualified relapses, at Week 24
    • Proportion of subjects who remain qualified relapse-free at Week 24
    • Change from Baseline in Expanded Disability Status Scale (EDSS) at Week 24
    • Safety as assessed by the nature, severity, and incidence of adverse events (AEs); vital signs; electrocardiograms (ECGs); absolute concentrations and change from Baseline in immunoglobulin (Ig) levels; absolute numbers and change from Baseline in B cells; and clinical laboratory safety parameters (duration of placebo treatment group is limited to 24 weeks).
    criterios de valoración secundarios clave para evaluar la eficacia y seguridad de M2951 en comparación con el placebo:
    • tasa anualizada de recaídas (ARR), sobre la base de las recaídas cualificados definidos en el protocolo, en la semana 24
    • La proporción de sujetos que conservar la etiqueta libre de recaída en la semana 24
    • cambio desde el inicio en Escala Ampliada del Estado de Discapacidad (EDSS) en la semana 24
    • Seguridad según la evaluación de la naturaleza, la gravedad y la incidencia de acontecimientos adversos (AA); signos vitales; electrocardiogramas (ECG); concentraciones absolutas y el cambio de línea de base en los niveles de inmunoglobulina (Ig); números absolutos y cambio desde el inicio en las células B; y los parámetros de seguridad de laboratorio clínico (duración del grupo de tratamiento con placebo se limita a 24 semanas).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 24 for the key secondary endpoints
    Semana 24 para los criterios de valoración secundarios clave
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    tolerability; determine the potential correlation between gene expression signatures and PD/efficacy
    tolerabilidad; determinar la correlación potencial entre las firmas de expresión génica y PD / eficacia
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial5
    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.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA59
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Bulgaria
    Croatia
    Czech Republic
    Poland
    Russian Federation
    Serbia
    Slovakia
    Spain
    Turkey
    Ukraine
    United Kingdom
    United States
    E.8.7Trial 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
    LSLV
    LSLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 248
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 250
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    4 week safety follow up after treatment. A separate open-label extension protocol will be developed allowing continued dosing, provided that safety and tolerability are acceptable.
    4 semanas de seguridad de seguimiento después del tratamiento. Se desarrollará un estudio abierto de extensión de protocolo independiente que ofrece un sguimiento continuado, siempre que la seguridad y la tolerabilidad sean aceptables
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-01-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-12-20
    P. End of Trial
    P.End of Trial StatusOngoing
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