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    Summary
    EudraCT Number:2010-024423-24
    Sponsor's Protocol Code Number:AB10015
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Prohibited by CA
    Date on which this record was first entered in the EudraCT database:2013-12-05
    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 ConcernedSlovakia - SIDC (Slovak)
    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)
    Prospektívna, multicentrická, randomizovaná, dvojito zaslepená, placebom kontrolovaná, s paralelnými skupinami, štúdia fázy 2/3 k porovnaniu účinnosti a bezpečnosti masitinibu oproti placebu v liečbe pacientov s amyotrofickou laterálnou sklerózou (ALS)
    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)
    Zhodnotenie masitinibu pri amyotropickej laterálnej skleróze (ALS)
    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)
    pacienti trpiaci amyotrofickou laterálnou sklerózou
    E.1.1.1Medical condition in easily understood language
    Amyotrophic Lateral Sclerosis (ALS)
    Amyotrofická laterálna skleróza (ALS)
    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).
    Cieľom je porovnanie účinnosti a bezpečnosti masitinibu v kombinácii s riluzolom oproti placebu v kombinácii s riluzolom v liečbe pacientov s amyotrofickou laterálnou sklerózou (ALS).
    E.2.2Secondary objectives of the trial
    • 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

    • Kombinované hodnotenie funkcie a prežitia (CAFS)
    • Prežitie definované ako čas od randomizácie do dátumu zdokumentovanej smrti alebo prvej tracheotómie
    • Čas do prvej tracheotómie definovaný ako čas od randomizácie do času prvej tracheotómie
    • Zmena vo vynútenej vitálnej kapacite (FVC) od baseline do každého časového bodu (týždeň 4, 8, 12, 24, 36, 48)
    • Počet zlyhaní definovaných ako 9-bodový pokles v ALSFRS-R od baseline alebo smrťou
    • Miera prežitia definovaná ako miera pacientov nažive bez tracheotómie v každom časovom bode
    (týždeň 12, 24, 36 a 48).
    • Zmena v úrovni cystatínu C v každom časovom bode
    • Čas do prvej gastrostómie definovaný ako čas od randomizácie do času prvej gastrostómie
    • Absolútna a relatívna zmena od baseline v ALSAQ-40 v každom časovom bode
    • Bezpečnosť: výskyt nežiaducich účinkov (AE), zmeny pri klinických vyšetreniach zahŕňajúce vitálne znaky a váhu, EKG a laboratórne testy (biochémia, hematológia a analýza moču).
    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.
    Farmakogenomická (PG) štúdia:
    Cieľom tejto štúdie je určenie génov polymorfizmu, vrátane HLA polymorfizmu ktoré by mohli byť asociované so zvýšeným rizikom ťažkej neutropénie alebo kožnej toxicity spôsobenej masitinibom. Všetky vzorky budú centrálne analyzované v Inštitúte Paoli Calmettes, oddelenie biopatológie, Marseille, Francúzsko.
    Farmakokinetická (PK) štúdia:
    Farmakokinetická štúdia zhodnotí PK parameter rilouzole u max. 10 pacientov.
    Všetky vzorky budú centrálne analyzované vo Farmakologickom laboratóriu, Centrum René Huguenin, Saint-Cloud, Francúzsko.
    E.3Principal 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. 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
    • and 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

    1. Pacientka alebo pacient vo veku medzi 18 a 75 rokmi, s váhou ˃ 50 kg a BMI medzi 18 a 35 kg/m2
    2. Familiárna alebo sporadická ALS
    3. Pacient s diagnostikovanou (laboratórne potvrdenou), klinicky pravdepodobnou alebo jednoznačnou ALS podľa aktualizovaných kritérií Svetovej Federácie Neurológie z EL Escorial (Brooks, 1994).
    4. Trvanie symptómov ochorenia od nástupu nie dlhšie než 36 mesiacov pred screeningovou návštevou
    5. Pacient liečený stabilnou dávkou riluzole (100mg/deň) po dobu aspoň 30 dní pred screeningovou návštevou
    6. Pacient s vynútenou vitálnou kapacitou rovnou alebo vyššou než 60% predpokladanej bežnej hodnoty pre dané pohlavie, výšku a vek pri screeningovej návšteve
    7. Pacient s očakávanou dĺžkou života ≥ 6 mesiacov
    8. Pacient s primeranou funkciou orgánov pri screeningovej a baseline návšteve:
    • Absolútny počet neutrofilov (ANC) ≥ 2 x 109/L
    • Hemoglobín ≥ 10 g/dL
    • Krvné doštičky (PTL) ≥ 100 x 109/L
    • AST/ALT ≤ 3 ULN
    • Bilirubín ≤ 1.5 ULN
    • Albuminémia > 1 x LLN
    • Kreatinínová klírens > 60 mL/min (Cockcroftov a Gaultov vzorec)
    • Proteinúria < 30 mg/dL (1+) na dipstick teste; v prípade preteinúrie ≥ 1+ na dipstick teste, 24 hodinová proteinúria musí byť < 1.5g/24 hodín
    9. Pacientky vo fertilnom veku (vstupujúce do štúdie po menštruácii a s negatívnym tehotenským testom) , ktoré súhlasia s používaním dvoch vysoko účinných metód lekársky prijateľnej antikoncepcie (jednej pre pacienta a jedna pre partnera) počas štúdie a počas 3 mesiacov po poslednom podaní študijnej medikácie. Prijateľné formy antikoncepcie sú:
    • Dokumentované zavedenie vnútromaternicového telieska (hormonálne/s meďou) alebo použitie bariérového spôsobu ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • Dokumentované podviazanie vaječníkov (ženská sterilizácia). Okrem toho by mal byť tiež používaný beriérový spôsob ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • Bariérová metóda: Kondóm a okluzívny kryt diafragma alebo cervikálny klobúčik) v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi
    • Akékoľvek iné metódy antikoncepcie so zdokumentovanou mierou zlyhania < 1 % za rok
    • Abstinencia
    10. Mužskí pacienti musia používať lekársky prijateľné formy antikoncepcie, pokiaľ je ich partnerka tehotná, alebo od doby prvého podania hodnoteného prípravku až do troch mesiacov po poslednej dávke skúšaného lieku. Prijateľné formy sú:
    • kondóm
    • chirurgická sterilizácia (vasektómia so zdokumentovanou azoospermiou) , je treba používať aj kondóm
    Mužskí pacienti musia počas štúdie a 3 mesiace po poslednej liečbe používať dve metódy lekársky prijateľnej vysoko účinnej antikoncepcie (jednu pacient a druhú partnerka). Prijateľné formy antikoncepcie sú:
    • kondóm alebo pesar (diafragma alebo cervikálny klobúčik) v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi.
    • chirurgická sterilizácia (vasektómia so zdokumentovanou azoospermiou) a bariérový spôsob ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • Vaša partnerka používa perorálnu antikoncepciu (kombinované tablety s estrogénom či progesterónom), injekcie progesterónu či podkožné implantáty a bariérový spôsob ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • lekárom predpísaná antikoncepčná náplasť a bariérová metóda (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/číapikmi).
    • Vaša partnerka podstúpila zdokumentované zavedenie vnútromaternicového telieska (hormonálne/s meďou) či použitie bariérového spôsobu ochrany ((kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • abstinencia iba pokiaľ je to v súlade s preferovaným a obvyklým životným štýlom subjektu
    11. Pacientka v plodnom veku musí mať negatívny tehotenský test na skríningu a baseline
    12. Pacient schopný a ochotný riadiť sa podľa pokynov protokolu
    13. Pacient schopný porozumieť informovanému súhlasu pacienta (a podpísať a datovať ho) pri screeningovej návšteve a pred akýmikoľvek procedúrami podľa protokolu

    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. Pacient s históriou hematologických, pečeňových, respiračných porúch, ktoré sú klinicky významné pre jeho/jej účasť v štúdii
    2. Pacient, ktorý podstúpil tracheotómiu a/alebo gastrostómiu
    3. Pacient s diagnózou rakoviny alebo so známkami pokračujúceho ochorenia v priebehu 5 rokov pred začiatkom študijnej liečby
    4. Pacient s významnými zmyslovými abnormalitami, demenciou, inými neurologickými ochoreniami, nekompenzovanými zdravotnými ochoreniami a s psychiatrickými ochoreniami
    5. Pacient, ktorý sa zúčastnil klinického výskumu v priebehu 3 mesiacov pred screeningovou návštevou
    6. Tehotná alebo dojčiaca pacientka
    7. Pacient so známou diagnózou infekcie vírusom ľudskej imunitnej nedostatočnosti (HIV)

    8. Pacient, o ktorom sa vie, že má hepatitídu typu B, hepatitídu typu C alebo tuberkulózu

    9. Pacient s akýmkoľvek vážnym a/alebo nekontrolovaným zdravotným ochorením
    10. Pacient so srdečným ochorením definovaným aspoň jednou z nasledujúcich podmienok:
    • Pacient s nedávnou srdečnou anamnézou (behom 6 mesiacov):
    - Akútny koronárny syndróm
    - Akútne zlyhanie srdca (typu III alebo IV klasifikácie NYHA)
    - Významná komorová arytmia (pretrvávajúca komorová tachykardia, komorová fibrilácia, resuscitácia z náhlej smrti)
    Pacient so zlyhaním srdca typu III alebo IV podľa klasifikácie NYHA
    • Pacient s vážnou poruchou vodivosti, ktorej nie je zabránené stálou stimuláciou (atrio-ventrikulárny blok 2 a 3, sino-atriálny blok)
    • Synkópa bez známej príčiny v priebehu 3 mesiacov
    • Nekontrolovaná ťažká hypertenzia, podľa úsudku skúšajúceho, alebo symptomatická hypertenzia
    11. Pacient s históriou zlej spolupráce alebo s históriou užívania drog/alkoholu, alebo nadmernej konzumácie alkoholických nápojov, ktorá by zasahovala do schopnosti riadiť sa študijným protokolom, alebo súčasná či minulá duševná choroba, ktorá môže zasahovať do schopnosti riadiť sa študijným protokolom, alebo podpísať informovaný súhlas.
    VYMÝVANIE PREDCHÁDZAJÚCEJ LIEČBY
    1. Pacient užívajúci akúkoľvek vyvíjanú látku v priebehu 3 mesiacov pred screeningovou návštevou.
    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
    Hlavný cieľ
    Zmena od baseline v týždni 48 v Revidovanej funkčnej stupnici hodnotenia amyotrofickej laterálnej sklerózy (ALSFRS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 48
    týždeň 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

    • Kombinované hodnotenie funkcie a prežitia (CAFS)
    • Prežitie definované ako čas od randomizácie do dátumu zdokumentovanej smrti alebo prvej tracheotómie
    • Čas do prvej tracheotómie definovaný ako čas od randomizácie do času prvej tracheotómie
    • Zmena vo vynútenej vitálnej kapacite (FVC) od baseline do každého časového bodu (týždeň 4, 8, 12, 24, 36, 48)
    • Počet zlyhaní definovaných ako 9-bodový pokles v ALSFRS-R od baseline alebo smrťou
    • Miera prežitia definovaná ako miera pacientov nažive bez tracheotómie v každom časovom bode
    (týždeň 12, 24, 36 a 48).
    • Zmena v úrovni cystatínu C v každom časovom bode
    • Čas do prvej gastrostómie definovaný ako čas od randomizácie do času prvej gastrostómie
    • Absolútna a relatívna zmena od baseline v ALSAQ-40 v každom časovom bode
    • Bezpečnosť: výskyt nežiaducich účinkov (AE), zmeny pri klinických vyšetreniach zahŕňajúce vitálne znaky a váhu, EKG a laboratórne testy (biochémia, hematológia a analýza moču).
    E.5.2.1Timepoint(s) of evaluation of this end point
    week 4, 8, 12, 24, 36
    týždeň 4, 8, 12, 24, 36
    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 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 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)
    Liečba bude ukončená v prípade:
    • Nedostatočnej účinnosti
    • Stiahnutia informovaného súhlasu
    • nežiaduceho alebo skrytého účinku považovaného pacientom za neprijateľný alebo nekompatibilný s pokračovaním v štúdii podľa skúšajúceho
    • Porušenie protokolu (napr. nedodržiavanie liečebného dávkovania, nutnosť nepovolenej liečby)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    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: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 81
    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 state81
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 300
    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
    bez zmeny
    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 Decision2014-04-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-02-17
    P. End of Trial
    P.End of Trial StatusProhibited by CA
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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