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    Summary
    EudraCT Number:2019-001862-13
    Sponsor's Protocol Code Number:AB19001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Temporarily Halted
    Date on which this record was first entered in the EudraCT database:2020-06-12
    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 number2019-001862-13
    A.3Full title of the trial
    A prospective, multicenter, randomised, double-blind, placebo-controlled, parallel groups, phase 3 study to compare the efficacy and safety of masitinib in combination with Riluzole versus placebo in combination with Riluzole in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS)
    Estudio Fase III, prospectivo, multicéntrico, randomizado, doble ciego, controlado con placebo y de grupos paralelos para comparar la eficacia y seguridad de masitinib en combinación con riluzol frente a placebo en combinación con riluzol para el tratamiento de pacientes con Esclerosis Lateral Amiotrófica (ELA).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluation of masitinib in Amyotrophic Lateral Sclerosis (ALS)
    Evaluación de masitinib en la esclerosis lateral amiotrófica (ELA)
    A.3.2Name or abbreviated title of the trial where available
    not applicable
    no aplica
    A.4.1Sponsor's protocol code numberAB19001
    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 SponsorABScience
    B.1.3.4CountryFrance
    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 supportABScience
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationABScience
    B.5.2Functional name of contact pointAlain Moussy
    B.5.3 Address:
    B.5.3.1Street Address3 avenue George V
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75008
    B.5.3.4CountryFrance
    B.5.4Telephone number00331472 02311
    B.5.5Fax number00331472 02411
    B.5.6E-maila.moussy@ab-science.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 namemasitinib
    D.3.2Product code AB1010
    D.3.4Pharmaceutical form Film-coated 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 INNMasitinib mesylate
    D.3.9.1CAS number 790-299-79-5
    D.3.9.2Current sponsor codeAB1010
    D.3.9.3Other descriptive namena
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 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 namemasitinib
    D.3.2Product code AB1010
    D.3.4Pharmaceutical form Film-coated 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 INNMasitinib mesylate
    D.3.9.1CAS number 790-299-79-5
    D.3.9.2Current sponsor codeAB1010
    D.3.9.3Other descriptive namena
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    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
    patients suffering from Amyotrophic Lateral Sclerosis (ALS)
    Pacientes que sufren de Esclerosis Lateral Amiotrófica (ELA)
    E.1.1.1Medical condition in easily understood language
    Amyotrophic Lateral Sclerosis (ALS)
    Esclerosis Lateral Amiotrófica (ELA)
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10002026
    E.1.2Term Amyotrophic lateral sclerosis
    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 demonstrate statistically significant improvement from baseline in ALSFRS-R after 48-week treatment of two doses of masitinib versus matching placebo in patients diagnosed with ALS treated with Riluzole.
    El objetivo principal es demostrar una mejora estadísticamente significativa desde el inicio en ALSFRS-R después de 48 semanas de tratamiento de dos dosis de masitinib versus placebo en pacientes diagnosticados con ELA tratados con Riluzol.
    E.2.2Secondary objectives of the trial
    Secondary objectives are to assess the efficacy and safety of two doses of masitinib versus matching placebo in the treatment of patients diagnosed with ALS treated with Riluzole
    Los objetivos secundarios son evaluar la eficacia y seguridad de dos dosis de masitinib versus placebo equivalente en el tratamiento de pacientes diagnosticados con ELA tratados con Riluzol
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Pharmacodynamic/biomarker(s):
    Identification of pharmacodynamic biomarker(s) is needed to fully characterize the potential disease modifying effects of masitinib in ALS patients.

    PharmacoGenomic (PG) study:
    Determination of the genetic polymorphisms, including HLA polymorphisms that could be associated with an increased risk of masitinib-induced severe neutropenia and severe skin toxicity

    PharmacoKinetic (PK) study:
    Measurement of pharmacokinetic parameters of masitinib and Riluzole in up to 10 ALS patients per group and validate population PK model for masitinib
    Farmacodinámica / biomarcadores:
    La identificación de biomarcadores farmacodinámicos es necesaria para caracterizar completamente los posibles efectos modificadores de la enfermedad de masitinib en pacientes con ELA.

    Estudio PharmacoGenomic (PG):
    Determinación de los polimorfismos genéticos, incluidos los polimorfismos de HLA que podrían estar asociados con un mayor riesgo de neutropenia grave inducida por masitinib y toxicidad cutánea grave

    Estudio farmacocinético (PK):
    Medición de los parámetros farmacocinéticos de masitinib y riluzol en hasta 10 pacientes con ELA por grupo y validar el modelo de población PK para masitinib
    E.3Principal inclusion criteria
    1. Patient, male or female, diagnosed with laboratory supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria [52]
    2. Patient with a familial or sporadic ALS
    3. Patient aged between 18 and 75 years old inclusive at screening
    4. Patient treated with a stable dose of Riluzole (100 mg/day) for at least 12 weeks prior to baseline visit
    5. Patient with an ALS disease duration from diagnosis no longer than 24 months at screening
    6. Patient with an ALSFRS-R total score progression between onset of the disease and screening of
    > 0.3 and <1.1 point/month
    7. Patient with an ALSFRS-R total score decrease of ≥ 1 point between screening and baseline
    8. Patient with an ALSFRS-R total score of at least 26 at screening following rules below:
    - at least 3 on item #3 and
    - at least 2 on each of the other 11 items (i.e. item #1, #2, #4, #5a or #5b, #6, #7, #8, #9, #10, #11 and #12)
    9. Patient with an ALSFRS-R total score of at least 25 at randomization following rules below:
    - at least 3 on item #3 and
    - at least 2 on each of the other 11 items (i.e. item #1, #2, #4, #5a or #5b, #6, #7, #8, #9, #10, #11 and #12)
    10. Contraception:
    - Female patient of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an effective method of contraception by her male partner during the study and for 3 months and a half after the last treatment intake
    - Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an effective method of contraception by his female partner during the study and for 3 months and a half after the last treatment intake OR who agrees to use an effective method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months and a half after the last treatment intake
    Highly effective and effective methods of contraception are detailed in appendix 15.1
    11. Patient able to understand, and willing to sign, and date the written informed consent form prior to any protocol-specific procedures. If patients are duly capable of study consent but are unable to sign by themselves due to aggravation of disease condition, written informed consent can be obtained from a legally authorized representative who can sign on behalf of the patients after confirming the patients' agreement to study participation.
    12. Patient able and willing to comply with study protocol and to come on-site as per protocol visits schedule
    13. Patient able to understand, and willing to follow the safety procedures mentioned on the patient card in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity
    1. Paciente, hombre o mujer, diagnosticado con ELA probable, clínicamente probable o definitivo con apoyo de laboratorio de acuerdo con los criterios revisados ​​de El Escorial de la Federación Mundial de Neurología [52]
    2. Paciente con una ELA familiar o esporádica
    3. Paciente con edades comprendidas entre 18 y 75 años inclusive en el examen
    4. Paciente tratado con una dosis estable de Riluzol (100 mg / día) durante al menos 12 semanas antes de la visita inicial
    5. Paciente con una duración de la enfermedad de ELA desde el diagnóstico no más de 24 meses en la selección
    6. Paciente con una progresión de la puntuación total ALSFRS-R entre el inicio de la enfermedad y la detección de
    > 0.3 y <1.1 punto / mes
    7. Paciente con una disminución de la puntuación total ALSFRS-R de ≥ 1 punto entre el cribado y el valor basal
    8. Paciente con un puntaje total ALSFRS-R de al menos 26 en el examen siguiendo las siguientes reglas:
    - al menos 3 en el ítem # 3 y
    - al menos 2 en cada uno de los otros 11 elementos (es decir, elemento # 1, # 2, # 4, # 5a o # 5b, # 6, # 7, # 8, # 9, # 10, # 11 y # 12)
    9. Paciente con una puntuación total ALSFRS-R de al menos 25 en la aleatorización siguiendo las siguientes reglas:
    - al menos 3 en el ítem # 3 y
    - al menos 2 en cada uno de los otros 11 elementos (es decir, elemento # 1, # 2, # 4, # 5a o # 5b, # 6, # 7, # 8, # 9, # 10, # 11 y # 12)
    10. Anticoncepción:
    - Paciente femenina en edad fértil (que ingresa al estudio después de un período menstrual y que tiene una prueba de embarazo negativa), que acepta utilizar un método anticonceptivo altamente efectivo y un método anticonceptivo efectivo por parte de su pareja masculina durante el estudio y durante 3 meses. y medio después de la última ingesta de tratamiento
    - Paciente masculino con una pareja femenina en edad fértil que acepta usar un método anticonceptivo altamente efectivo y un método anticonceptivo efectivo por parte de su pareja femenina durante el estudio y durante 3 meses y medio después de la última toma de tratamiento O que acepta usar un método anticonceptivo efectivo y un método anticonceptivo altamente efectivo por parte de su pareja femenina durante el estudio y durante 3 meses y medio después de la última toma de tratamiento
    Los métodos anticonceptivos altamente efectivos y detallados se detallan en el apéndice 15.1
    11. Paciente capaz de comprender y dispuesto a firmar y fechar el formulario de consentimiento informado por escrito antes de cualquier procedimiento específico del protocolo. Si los pacientes están debidamente capacitados para el consentimiento del estudio pero no pueden firmar por sí mismos debido al agravamiento de la enfermedad, se puede obtener el consentimiento informado por escrito de un representante legalmente autorizado que puede firmar en nombre de los pacientes después de confirmar el acuerdo de los pacientes para participar en el estudio. .
    12. Paciente capaz y dispuesto a cumplir con el protocolo del estudio y venir al sitio según el calendario de visitas del protocolo
    13. Paciente capaz de comprender y dispuesto a seguir los procedimientos de seguridad mencionados en la tarjeta del paciente en caso de signos o síntomas de neutropenia grave o toxicidad cutánea grave.
    E.4Principal exclusion criteria
    1. Patient with dementia or significant neurological, psychiatric, systemic or organic disease, uncontrolled or that may interfere with the conduct of the trial or its results
    2. Patient with hypersensitivity to masitinib excipients
    3. Patient with an FVC < 60% predicted normal value for gender, height, and age at screening
    4. Patient with a weight < 41 kg and a BMI < 21 or > 30 kg/m² at screening and at baseline
    5. Pregnant, or nursing female patient
    6. Patient with history (or family history) of severe skin toxicities or reactions
    7. Patients treated by drugs known to be at high risk for Stevens-Johnson Syndrome or for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome
    8. Patient with history of severe bone marrow disorders such as agranulocytosis or aplasia, or with abnormal laboratory results from local laboratory assessments at screening and baseline :
    - Neutropenia with ANC < 1.5x109/L
    - Anemia with Hgb < LLN and red blood cell count below the LLN
    - Thrombocytopenia with platelets counts < 150 x 109/L
    9. Patient with history of hepatic disorders, with a known liver disease or alcohol abuse, or with abnormal laboratory results from local laboratory assessments defined as:
    - hepatic transaminase levels > 2 ULN at baseline, or
    - total bilirubin level > 1.5 ULN at baseline, or
    - both hepatic transaminase levels and total bilirubin level outside of the normal ranges at screening and baseline, or
    - albuminemia < 1 x LLN at screening and baseline
    10. Patient with pre-existing severe renal impairment, or with abnormal laboratory results from local laboratory assessments at screening and baseline :
    - Creatinine clearance < 60 mL/min (Cockcroft and Gault formula)
    - Proteinuria > 30 mg/dL (1+) on dipstick; in case of the proteinuria ≥ 1+ on the dipstick, 24 hours proteinuria must be > 1.5g/24 hours
    11. Patient with active severe infection such as herpes, tuberculosis, viral hepatitis, human immunodeficiency virus infection
    12. Patient with autoimmune conditions such as systemic lupus erythematosus
    13. Patient with a diagnosis of cancer or evidence of continued disease within five years before screening
    14. Patient with severe cardiac conditions:
    - Patient with recent history of severe cardiovascular conditions including acute myocardial infarction, unstable angina pectoris, coronary revascularization procedure, congestive heart failure of NYHA Class III or IV, stroke, including a transient ischemic attack
    - Patient with cardiac conduction abnormalities at study entry including a QTc Fredericia interval >450 milliseconds for males and >470 milliseconds for females, a second- or third-degree atrioventricular block not successfully treated with a pacemaker
    - Patient presenting with edema of cardiac origin and left ventricular ejection fraction ≤ 50%
    15. Patient with risk factors for sudden unexpected death of cardiovascular origin
    16. Patient who has been exposed to an investigational treatment within 3 months prior to screening
    17. Patient who has been exposed to Edaravone within at least 30 days prior to screening
    18. Patient treated concomitantly with drugs known to interact with cytochrome P450 (CYP450) isoenzymes (2C9, 2D6 and 3A4)
    1. Paciente con demencia o enfermedad neurológica, psiquiátrica, sistémica u orgánica significativa, no controlada o que pueda interferir con la realización del ensayo o sus resultados.
    2. Paciente con hipersensibilidad a los excipientes de masitinib
    3. Paciente con un FVC <60% del valor normal pronosticado para sexo, altura y edad en el examen
    4. Paciente con un peso <41 kg y un IMC <21 o> 30 kg / m² en el cribado y al inicio
    5. Paciente embarazada o lactante
    6. Paciente con antecedentes (o antecedentes familiares) de toxicidades o reacciones cutáneas graves.
    7. Pacientes tratados con medicamentos que se sabe que tienen un alto riesgo de síndrome de Stevens-Johnson o de reacción a medicamentos con síndrome de eosinofilia y síntomas sistémicos (DRESS)
    8. Paciente con antecedentes de trastornos severos de la médula ósea, como agranulocitosis o aplasia, o con resultados anormales de laboratorio de evaluaciones de laboratorio locales en la detección y en la evaluación inicial:
    - Neutropenia con ANC <1.5x109 / L
    - Anemia con Hgb <LLN y recuento de glóbulos rojos por debajo del LLN
    - Trombocitopenia con recuentos de plaquetas <150 x 109 / L
    9. Paciente con antecedentes de trastornos hepáticos, con una enfermedad hepática conocida o abuso de alcohol, o con resultados de laboratorio anormales de evaluaciones de laboratorio locales definidas como:
    - niveles de transaminasas hepáticas> 2 ULN al inicio del estudio, o
    - nivel de bilirrubina total> 1.5 ULN al inicio del estudio, o
    - tanto los niveles de transaminasa hepática como el nivel de bilirrubina total fuera de los rangos normales en la detección y en la evaluación inicial, o
    - albuminemia <1 x LLN en el cribado y la línea de base
    10. Paciente con insuficiencia renal grave preexistente, o con resultados de laboratorio anormales de las evaluaciones de laboratorio locales en la detección y la línea de base:
    - Depuración de creatinina <60 ml / min (fórmula de Cockcroft y Gault)
    - Proteinuria> 30 mg / dL (1+) en la tira reactiva; en caso de proteinuria ≥ 1+ en la tira reactiva, la proteinuria de 24 horas debe ser> 1,5 g / 24 horas
    11. Paciente con infección activa activa, como herpes, tuberculosis, hepatitis viral, infección por el virus de la inmunodeficiencia humana.
    12. Paciente con afecciones autoinmunes como lupus eritematoso sistémico.
    13. Paciente con diagnóstico de cáncer o evidencia de enfermedad continua dentro de los cinco años previos a la detección.
    14. Paciente con afecciones cardíacas graves:
    - Paciente con antecedentes recientes de afecciones cardiovasculares graves, incluido infarto agudo de miocardio, angina de pecho inestable, procedimiento de revascularización coronaria, insuficiencia cardíaca congestiva de NYHA Clase III o IV, accidente cerebrovascular, incluido un ataque isquémico transitorio
    - Paciente con anomalías en la conducción cardíaca al inicio del estudio, incluido un intervalo QTc Fredericia> 450 milisegundos para hombres y> 470 milisegundos para mujeres, un bloqueo auriculoventricular de segundo o tercer grado no tratado con éxito con un marcapasos
    - Paciente con edema de origen cardíaco y fracción de eyección del ventrículo izquierdo ≤ 50%
    15. Paciente con factores de riesgo de muerte súbita inesperada de origen cardiovascular.
    16. Paciente que ha estado expuesto a un tratamiento de investigación dentro de los 3 meses previos a la detección.
    17. Paciente que ha estado expuesto a Edaravona al menos 30 días antes del examen
    18. Paciente tratado concomitantemente con fármacos conocidos por interactuar con isoenzimas del citocromo P450 (CYP450) (2C9, 2D6 y 3A4)
    E.5 End points
    E.5.1Primary end point(s)
    Absolute Change from baseline to week 48 in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised total score
    Cambio absoluto desde el inicio hasta la semana 48 en la escala de calificación funcional de la esclerosis lateral amiotrófica (ALSFRS) - Puntaje total revisado
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 48
    semana 48
    E.5.2Secondary end point(s)
    - Progression free survival (PFS) defined as the time from randomization to progression (decline of more than 9 points in ALSFRS-R score from baseline) or death
    - Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSAQ-40) change
    - Forced Vital Capacity (FVC) change
    - Upper- and lower-limb muscle strength using hand-held dynamometry (HHD)
    - Clinician-rated Clinical Global Impression (CGI)
    - Combined Assessment of Function and Survival (CAFS)
    - Overall Survival (OS)
    - Event free survival (EFS) defined as the time from randomization to the first occurrence of either death or tracheostomy

    Safety Analysis:
    - Adverse events
    - Vital signs, physical examination, ECGs
    - Clinical laboratory tests (haematology, biochemistry, urinalysis and urinary cytology)
    - Supervivencia libre de progresión (SLP) definida como el tiempo desde la aleatorización hasta la progresión (disminución de más de 9 puntos en la puntuación ALSFRS-R desde el inicio) o la muerte
    - Cambio en el cuestionario de evaluación de la esclerosis lateral amiotrófica 40 (ALSAQ-40)
    - Cambio de capacidad vital forzada (FVC)
    - Fuerza muscular de las extremidades superiores e inferiores mediante dinamometría manual (HHD)
    - Impresión Clínica Global Clínica (CGI)
    - Evaluación combinada de la función y la supervivencia (CAFS)
    - Supervivencia general (OS)
    - Supervivencia libre de eventos (EFS) definida como el tiempo desde la aleatorización hasta la primera aparición de muerte o traqueotomía

    Análisis de seguridad:
    - Eventos adversos
    - Signos vitales, examen físico, ECG
    - Pruebas de laboratorio clínico (hematología, bioquímica, análisis de orina y citología urinaria)
    E.5.2.1Timepoint(s) of evaluation of this end point
    at W48 or event occurence (death) depending on secondary endpoint
    en semana 48 u ocurrencia del evento (muerte) dependiendo del punto final secundario
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 trial3
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA29
    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 Yes
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Belgium
    Canada
    Denmark
    France
    Germany
    Ireland
    Israel
    Italy
    Netherlands
    Poland
    Portugal
    Russian Federation
    Slovenia
    Spain
    Sweden
    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
    LVLS
    Última visita del último sujeto
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    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: 450
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 state55
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 495
    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)
    Patients will be treated in accordance with the prevailing standard of medical care.
    Los pacientes serán tratados de acuerdo con la atención médica habitual.
    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 Decision2020-09-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-09-11
    P. End of Trial
    P.End of Trial StatusTemporarily Halted
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