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    Summary
    EudraCT Number:2010-024423-24
    Sponsor's Protocol Code Number:AB10015
    National Competent Authority:Portugal - INFARMED
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-11-03
    Trial results View 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 ConcernedPortugal - INFARMED
    A.2EudraCT number2010-024423-24
    A.3Full title of the trial
    A prospective, multicenter, randomized, double-blind, placebocontrolled, parallel groups, phase 2/3 study to compare the efficacy and safety of masitinib versus placebo in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS)
    Um estudo de fase 2/3 prospetivo, multicêntrico, randomizado, duplo-cego, controlado por placebo, de grupos paralelos, é conduzido para comparar a eficácia e segurança do Masitinib contra placebo no tratamento de pacientes com Esclerose 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)
    Avaliação do masitinib em Esclerose Lateral Amiotrófica
    A.3.2Name or abbreviated title of the trial where available
    not applicable
    A.4.1Sponsor's protocol code numberAB10015
    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 number0033147 20 30 08
    B.5.5Fax number0033147 20 24 11
    B.5.6E-mailalain.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.3.8 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.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 number100
    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 sofrem de esclerose lateral amiotrófica
    E.1.1.1Medical condition in easily understood language
    Amyotrophic Lateral Sclerosis (ALS)
    Esclerose 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 20.0
    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 objective is to compare the efficacy and safety of masitinib versus placebo in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS).
    O objetivo é comparar a eficácia e segurança do Masitinib em combinação com Riluzol versus placebo em combinação com Riluzol no tratamento de pacientes que sofrem de Esclerose Lateral Amiotrófica (ELA).
    E.2.2Secondary objectives of the trial
    not applicable
    não aplicável
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    PharmacoGenomic (PG) study:
    The aim of this study is to determine the genes polymorphisms, including HLA polymorphismsn that could be associated with an increase risk of masitinib-induced severe neutropenia and severe skin toxicity. All samples will be centrally analyzed in the Institut Paoli Calmettes, department de Biopathologie, Marseille, France.

    PharmacoKinetic (PK) study:
    A Pharmacokinetic study, in up to 10 patients, to evaluate PK parameters of riluzole will be conducted.
    All samples will be centrally analysed in the Pharmacology Laboratory, Centre René Huguenin, Saint-Cloud,
    France.
    Estudo farmacogenómico (PG):

    O objetivo deste estudo é determinar os polimorfismos dos genes, incluindo polimorfismo HLA que pode estar associado a um aumento do risco de neutropenia grave induzida por Masitinib e toxicidade cutânea grave. Todas as amostras serão analisadas de forma centralizada no Institut Paoli Calmettes, departamento de Biopatologia, Marselha, França.


    Estudo farmacocinético (PK):

    Será realizado um estudo farmacocinético em até 10 pacientes para avaliar os parâmetros PK do Riluzol.
    Todas as amostras serão analisadas de forma centralizada no Laboratório de Farmacologia do Centro René Huguenin, Saint-Cloud, França.
    E.3Principal inclusion criteria
    INCLUSION CRITERIA:
    1. Female or male patient aged between 18 and 75 years of age, with a weight > 50 kg and BMI between 18 and 35 kg/m².
    2. Familial or sporadic ALS
    3. Patient diagnosed with laboratory supported, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria (Brooks, 1994)
    4. Disease duration from symptoms onset no longer than 36 months at the screening visit
    5. Patient treated with a stable dose of riluzole (100 mg/day) for at least 30 days prior to screening
    6. Patient with a FVC (Forced Vital Capacity) equal to or more than 60% predicted normal value for gender, height, and age at the screening visit
    7. Patient with life expectancy ≥ 6 months
    8. Patient with adequate organ function at screening and baseline:
    • Absolute Neutrophils Count (ANC) ≥ 2 x 109/L
    • Hemoglobin ≥ 10 g/dL
    • Platelets (PTL) ≥ 100 x 109/L
    • AST/ALT ≤ 3 ULN
    • Bilirubin ≤ 1.5 ULN
    • Albuminemia > 1 x LLN
    • 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
    9. 9.Female patient of childbearing potential (entering the study after a
    menstrual period and who have a negative pregnancy test), who agrees
    to use two highly effective methods (one for the patient and one for the
    partner) of medically acceptable forms of contraception during the study
    and for 3 months after the last treatment intake. Acceptable forms of
    contraception include:
    •A documented placement of an intrauterine device (hormonal/copper)
    and the use of a barrier method (condom or occlusive cap [diaphragm or
    cervical/vault caps] used with spermicidal
    foam/gel/film/cream/suppository)
    •Documented tubal ligation (female sterilization). In addition, a barrier
    method (condom or occlusive cap [diaphragm or cervical/vault caps]
    used with spermicidal foam/gel/film/cream/suppository) should also be
    used
    •Barrier method: Condom and occlusive cap (diaphragm or
    cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
    any other contraceptive method with a documented failure rate of <1%
    per year
    •Abstinence only when this is in line with the preferred and usual
    lifestyle of the subject.
    10.Male patients must use medically acceptable methods of
    contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following
    administration of the last dose of study drug. Acceptable methods
    include:
    • Condom; •If you have undergone surgical sterilization (vasectomy
    with documentation of azoospermia) a condom should also be used.
    Male patients must use two highly effective methods (one for the patient
    and one for the partner) of medically acceptable forms of contraception
    during the study and for 3 months after the last treatment intake. The
    acceptable methods of contraception are as follows: •Condom and
    occlusive cap (diaphragm or cervical/vault caps) with spermicidal
    foam/gel/film/cream/suppository;
    •Surgical sterilization (vasectomy with documentation of azoospermia)
    and a barrier method (condom or occlusive cap [diaphragm or
    cervical/vault caps] used with spermicidal
    foam/gel/film/cream/suppository);
    •Your female partner uses oral contraceptives (combination oestrogen /
    progesterone pills), injectable progesterone or subdermal implants and a
    barrier method (condom or occlusive cap [diaphragm or cervical/vault
    caps] used with spermicidal foam/gel/film/cream/suppository);
    •Medically prescribed topically-applied transdermal contraceptive patch
    and a barrier method (condom or occlusive cap [diaphragm or
    cervical/vault caps] used with spermicidal
    foam/gel/film/cream/suppository);
    •Your female partner has undergone documented tubal ligation (female
    sterilization). In addition, a barrier method (condom or occlusive cap
    [diaphragm or cervical/vault caps] used with spermicidal
    foam/gel/film/cream/suppository) should also be used;
    •Your female partner has undergone documented placement of an
    intrauterine device (hormonal/copper) and the use of a barrier method
    (condom or occlusive cap [diaphragm or cervical/vault caps] used with
    spermicidal foam/gel/film/cream/suppository);
    •Abstinence only when this is in line with the preferred and usual
    lifestyle of the subject.
    11. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline
    12. Patient able and willing to comply with study procedures as per protocol
    13. Patient able to understand, and willing to sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
    14. 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, during the first two months of treatment
    Amended criteria:
    9. Paciente do sexo feminino com potencial fertilidade (ao entrarem no estudo após um período menstrual e que têm um teste de gravidez negativo), que concorde em usar dois métodos altamente eficazes (um para o paciente e outro para o parceiro) de formas de contracepção medicamente aceitáveis durante o estudo e para os 3 meses após a última toma do tratamento. Formas aceitáveis e contracepção incluem: • A colocação documentada de um dispositivo intra-uterino (hormonal / DIU) e a utilização de um método de barreira (preservativos ou diafragama pessário [diafragma ou tampões cervicais] usados com espuma / gel / pelicula / supositório / creme espermicida) • Laqueação documentada (esterilização feminina). Além disso, um método de barreira (preservativos ou diafragma-pessário [diafragma ou tampões cervicais] usado com espermicida em espuma / gel / pelicula / creme / supositório) também deve ser usado • Método de barreira: Preservativo e diafragma-pessário (diafragma ou tampão cervical) com espermicida em espuma / gel / pelicula / creme / supositório e qualquer outro método contraceptivo com uma taxa de falha documentada de <1% ao ano
    • Abstinência somente quando este está em linha com o estilo de vida preferido e usual do individuo. 10. Pacientes do sexo masculino devem utilizar métodos de contracepção medicamente aceitáveis, se a sua parceira está grávida, a partir do momento da primeira administração do fármaco em estudo até três meses após a administração da última dose do fármaco em estudo. Os métodos aceitáveis incluem:• Preservativo;• Se tiver sido submetido a esterilização cirúrgica (vasectomia com documentação de azoospermia) um preservativo deve ser usado também. Pacientes do sexo masculino devem usar dois métodos altamente eficazes (um para o paciente e outro para a parceira) de formas de contracepção clinicamente aceitáveis durante o estudo e durante 3 meses após a última toma do tratamento. Os métodos aceitáveis de contracepção são como se segue: • Preservativo e diafragma-pessário (diafragma ou tampão cervical) com espermicida em espuma / gel / pelicula / creme / supositório; • A esterilização cirúrgica (vasectomia com documentação de azoospermia) e um método de barreira (preservativos ou diafragma-pessário [diafragma ou tampão cervical] com espermicida em espuma / gel / pelicula / creme / supositório);
    • A sua parceira usa contraceptivos orais (combinação de pílulas de estrogênio / progesterona), progesterona injetável ou implantes subcutâneos e um método de barreira (preservativos ou diafragma-pessário [diafragma ou tampão cervical] com espermicida em espuma / gel / pelicula / creme / supositório); • Um sistema transdérmico contraceptivo medicamente prescrito aplicado topicamente e um método de barreira (preservativos ou diafragma-pessário [diafragma ou tampão cervical] com espermicida em espuma / gel / pelicula / creme / supositório);• A sua parceira sofreu laqueação documentada (esterilização feminina). Além disso, um método de barreira (preservativos ou diafragma-pessário [diafragma ou tampão cervical] com espermicida em espuma / gel / pelicula / creme / supositório) também deve ser usado;
    • A sua parceira sofreu colocação documentada de um dispositivo intra-uterino (hormonal / DIU) e o uso de um método de barreira (preservativos ou diafragma-pessário [diafragma ou tampão cervical] com espermicida em espuma / gel / pelicula / creme / supositório);• Abstinência somente quando esta está em linha com o estilo de vida preferido e usual do indivíduo.
    E.4Principal exclusion criteria
    EXCLUSION CRITERIA
    1. Patient with history of hematologic, hepatic, respiratory disorder that is clinically significant for his/her participation in the study
    2. Patient who underwent tracheotomy and /or gastrostomy
    3. Patient with a diagnosis of cancer or evidence of continued disease within five years before starting study treatment
    4. Patient with significant sensory abnormalities, dementia, other neurologic diseases, uncompensated medical illness and psychiatric illness
    5. Patient who have participated in a clinical trial within 3 months prior to screening
    6. Pregnant, or nursing female patient
    7. Patient with a known diagnosis of human immunodeficiency virus (HIV) infection
    8. Patient with known hepatitis B, hepatitis C or tuberculosis
    9. Patient with any severe and/or uncontrolled medical condition
    10. Patient having cardiac disorders defined by at least one of the following conditions:
    • Patient with recent cardiac history (within 6 months) of:
    - Acute coronary syndrome
    - Acute heart failure (class III or IV of the NYHA classification)
    - Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
    • Patient with cardiac failure class III or IV of the NYHA classification
    • Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
    • Syncope without known aetiology within 3 months
    • Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
    11. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
    PREVIOUS TREATMENTS WASH OUT
    12. Patient treated with any investigational agent within 3 months prior to screening
    1. Paciente com histórico de distúrbios hematológicos, hepáticos, respiratórios que sejam clinicamente significativos para a sua participação no estudo
    2. Paciente que foi submetido a traqueotomia e/ou gastrostomia
    3. Paciente com diagnóstico de cancro ou sinais de doença prolongada no prazo de cinco anos antes de iniciar o tratamento
    4. Paciente com significativas anormalidades sensitivas, demência e outras doenças neurológicas, doenças médicas descompensadas e doenças psiquiátricas
    5. Paciente que participou num ensaio clínico num prazo de 3 meses antes da triagem
    6. Paciente do sexo feminino gestante ou lactante
    7. Paciente com diagnóstico conhecido de infeção por vírus de imunodeficiência humana (HIV)
    8. Paciente com hepatite B, hepatite C ou tuberculose ativas conhecidas.
    9. Paciente com qualquer condição clínica grave e/ou não controlada
    10. Paciente com doenças cardíacas definidas por, no mínimo, uma das seguintes condições:
    • Paciente com histórico cardíaco recente (em 6 meses) de:

    - Síndrome coronária aguda

    - Insuficiência cardíaca aguda (classe III ou IV da classificação NYHA)

    - Arritmia ventricular significativa (taquicardia ventricular persistente, fibrilação ventricular, ressuscitação de morte súbita.
    • Paciente com insuficiência cardíaca de classe III ou IV da classificação NYHA
    • Paciente com distúrbios graves do sistema de condução não prevenidos por ritmo permanente (bloqueio atrioventricular 2 e 3, bloqueio sino-atrial)
    • Síncope sem etiologia conhecida em 3 meses
    • Hipertensão grave não controlada, segundo avaliação do investigador ou hipertensão sintomática
    11. Paciente com histórico de baixa aderência ou histórico de abuso de drogas/álcool, ou consumo excessivo de bebidas alcoólicas que possa interferir na capacidade de cumprir o protocolo do estudo, ou doença psiquiátrica atual ou passada que possa interferir na capacidade de cumprir o protocolo do estudo ou fornecer consentimento informado

    LINHAS DE TRATAMENTO PRÉVIAS
    12. Pacientes tratados com qualquer agente investigacional num prazo de 3 meses antes da triagem
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoints
    Change from baseline to week 48 in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised
    Alteração desde a consulta inicial até à semana 48 na escala funcional de avaliação revista da Esclerose Lateral Amiotrófica (ALSFRS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 48
    semana 48
    E.5.2Secondary end point(s)
    • Combined Assessment of Function and Survival (CAFS)
    • Survival defined as the time from randomisation to the date of documented death or first tracheotomy
    • Time to first tracheotomy defined as the time from randomisation to the time of the first tracheotomy
    • Change of Forced Vital Capacity (FVC) from baseline to each time point (week 4, 8, 12, 24, 36, 48)
    • Number of failure defined as a 9-point drop in ALSFRS-R from
    baseline or death
    • Change from baseline to each time point (week 4, 8, 12, 24 and 36) in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised
    • Survival rate defined as the rate of patients alive without tracheotomy at each time point (week 12, 24, 36 and 48)
    • Change in cystatin C level from baseline to each time point
    • • Time to first gastrostomy defined as the time from randomisation to
    the time of the first gastrostomy
    • Absolute and relative change from baseline in ALSAQ- 40 at each time
    point
    • Safety: occurrence of Adverse Events (AE), changes on clinical examination including vital signs and weight, ECG and laboratory exams (biochemistry, hematology and urinalysis)
    • Avaliação combinada da função e sobrevivência (CAFS)
    • A sobrevivência é definida como o tempo desde a randomização até à data do óbito documentado ou da primeira traqueotomia
    • Tempo para a primeira traqueotomia definido a partir da data da randomização até à data da primeira traqueotomia
    • Alteração da Capacidade Vital Forçada (CVF) desde a consulta inicial até cada tempo (semana 4, 8, 12, 24, 36, 48)
    • Número de falhas definido como uma descida de 9 pontos em ALSFRS-R desde a consulta inicial ou morte
    • Alteração desde a consulta inicial até a cada tempo (semana 4, 8, 12, 24 e 36) na escala funcional de avaliação revista da Esclerose Lateral Amiotrófica (ALSFRS)
    • Taxa de sobrevivência é definida como a taxa de pacientes vivos sem traqueotomia em cada tempo (semana 12, 24,
    36 e 48)
    • Mudança no nível de cistatina C desde a consulta inicial até cada tempo
    • Tempo para a primeira gastrectomia definida como a data desde a randomização até à data da primeira gastrectomia
    . Alteração absoluta e relativa desde consulta inicial em ALSAQ-40 em cada tempo
    • Segurança: ocorrência de efeitos secundários (ESs), alterações no exame físico incluindo sinais vitais e peso, ECG e exames laboratoriais (bioquímica, hematologia, análise de urina)
    E.5.2.1Timepoint(s) of evaluation of this end point
    weeks 4, 8, 12, 24, 36, 48
    semanas 4, 8, 12, 24, 36, 48
    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 No
    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) Yes
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA37
    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
    Colombia
    Czech Republic
    France
    Germany
    Greece
    Hungary
    Italy
    Mexico
    Romania
    Serbia
    Slovakia
    Spain
    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
    Study treatment will be discontinued in case of:
    . Lack of efficacy
    · Informed consent withdrawal
    · Adverse or undercurrent event considered intolerable by the patient or incompatible with continuation of
    the study according to the investigator
    · Protocol violation (e.g., noncompliance with treatment administration, prohibited treatment needed)
    Tratamento do estudo será interrompido em caso de:
    • Falta de eficácia
    • Revogação de consentimento informado
    • Evento adverso ou tendência considerado intolerável pelo paciente ou incompatíveis com a continuação do estudo de acordo com o investigador
    • violação de protocolo (descumprimento de administração do tratamento, tratamento proibido necessário)
    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: 360
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 21
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 240
    F.4.2.2In the whole clinical trial 381
    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)
    not different
    não diferente
    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 Decision2015-01-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-04-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-03-05
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