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    Summary
    EudraCT Number:2014-001579-30
    Sponsor's Protocol Code Number:TV5600-CNS-20006
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-09-19
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-001579-30
    A.3Full title of the trial
    A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Once Daily Oral Administration of Laquinimod (0.6 or 1.5 mg) in Patients with Primary Progressive Multiple Sclerosis (PPMS)
    Studio multinazionale, multicentrico, randomizzato, in doppio cieco, a gruppi paralleli, controllato con placebo per valutare l'efficacia, la sicurezza e la tollerabilità della somministrazione per via orale una volta al giorno di Laquinimod (0,6 o 1,5 mg) in pazienti affetti da sclerosi multipla primaria progressiva (SMPP)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 clinical study in subjects with Progressive Multiple Sclerosis to assess the efficacy, safety and tolerability of two oral doses of laquinimod either of 0.6 mg/day or 1.5mg/day (experimental drug) as
    compared to placebo
    Studio clinico di Fase 2 in soggetti con sclerosi multipla progressiva per valutare l’efficacia, la sicurezza e la tollerabilità della somministrazione per via orale di due dosi di laquinimod da 0,6 mg/die o 1,5 mg/die (farmaco sperimentale) quando messo a confronto con placebo
    A.3.2Name or abbreviated title of the trial where available
    ARPEGGIO
    A.4.1Sponsor's protocol code numberTV5600-CNS-20006
    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 SponsorTeva Pharmaceutical Industries Ltd.
    B.1.3.4CountryIsrael
    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 supportTeva Pharmaceutical Industries Ltd
    B.4.2CountryIsrael
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTeva Pharma GmbH
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressWaldeckerstrasse 7
    B.5.3.2Town/ cityMoerfelden-Walldorf
    B.5.3.3Post code64546
    B.5.3.4CountryGermany
    B.5.4Telephone number000000000000
    B.5.5Fax number000000000000
    B.5.6E-mailInfo-era-clinical@teva.de
    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 nameLaquinimod
    D.3.2Product code TV-5600
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLAQUINIMOD
    D.3.9.1CAS number 248282-07-7
    D.3.9.2Current sponsor codeTV-5600
    D.3.9.3Other descriptive nameLaquinimod Sodium (USAN)
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.6
    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 nameLaquinimod
    D.3.2Product code TV-5600
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLAQUINIMOD
    D.3.9.1CAS number 248282-07-7
    D.3.9.2Current sponsor codeTV-5600
    D.3.9.3Other descriptive nameLaquinimod Sodium (USAN)
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.5
    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 placeboCapsule, hard
    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
    Primary Progressive Multiple Sclerosis
    Sclerosi multipla primaria progressiva
    E.1.1.1Medical condition in easily understood language
    Primary Progressive Multiple Sclerosis (PPMS) is an autoimmune disease of the central nervous system featuring gradual worsening of neurological function without distinct exacerbations.
    La sclerosi multipla primaria progressiva (SMPP) è una malattia autoimmune del sistema nervoso centrale con progressivo peggioramento della funzione neurologica, senza esacerbazioni distinte.
    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 17.0
    E.1.2Level PT
    E.1.2Classification code 10063401
    E.1.2Term Primary progressive multiple 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 objectives of this study are to assess the efficacy, safety, and tolerability of a once daily oral dose
    of laquinimod (0.6 or 1.5 mg) compared to placebo in PPMS patients.
    gli obiettivi di questo studio sono le valutazioni di efficacia, sicurezza e tollerabilità della dose orale giornaliera di laquinimod una volta al giorno (0,6 o 1,5 mg) rispetto al placebo nei pazienti con SMPP.
    E.2.2Secondary objectives of the trial
    Not applicable
    Non applicabile
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Sub-studies (Ancillary studies) are described within the current core study protocol.
    Some of these studies may be performed only in selected sites and in accordance with local regulations as applicable.

    1. Pharmacokinetc Variables: Pharmacokinetics of laquinimod will be evaluated
    2. Potential Biomarker Measures: Potential biomarker assessments to better understand laquinimod MoA, as well as to explore response predictive markers for efficacy or safety
    3.Pharmacogenomic Variables: PGx analyses to investigate the association between genetic sequence polymorphisms and/or gene and clinical response including unexpected adverse events.
    4. Cerebrospinal fluid (CSF) assessment: to explore putative neuroprotective effects of laquinimod
    5. Optical coherence tomography (OCT) assessment: used as a tool for visualizing the processes of
    neurodegeneration, neuroprotection, and neurorepair in MS.
    I sottostudi (studi ancillari) sono descritti all’interno dell’attuale protocollo dello studio principale.
    Alcuni di questi studi possono essere effettuati solo presso centri selezionati e in conformità alle normative locali, ove applicabile.

    1. Variabili farmacocinetiche: Sarà valutata la farmacocinetica di laquinimod
    2. Parametri dei biomarcatori potenziali: Valutazioni dei biomarcatori potenziali per comprendere meglio il meccanismo di azione di laquinimod, nonché per esplorare i marcatori predittivi della risposta per l’efficacia o la sicurezza
    3. Variabili farmacogenomiche: Analisi PGx per valutare l’associazione tra polimorfismi genetici di sequenza e/o i geni e la risposta clinica compresi gli eventi avversi inattesi.
    4. Valutazione del liquido cerebrospinale (Cerebrospinal fluid, CSF): per esplorare gli effetti neuroprotettivi putativi di laquinimod
    5. Valutazione della tomografia a coerenza ottica (Optical coherence tomography, OCT): utilizzato come strumento per la visualizzazione dei processi di neurodegenerazione, neuroprotezione e neuroriparazione nella SM.
    E.3Principal inclusion criteria
    1. Patients must have a confirmed and documented PPMS diagnosis as defined by the current valid McDonald criteria
    2. Baseline magnetic resonance imaging (MRI) showing lesions consistent with PPMS in either or both brain and spinal cord
    3. Patients must have an Expanded Disability Status Scale (EDSS) score of 3 to 6.5, inclusive, at both
    screening and baseline visits
    4. Documented evidence of clinical disability progression in the 2 years prior to screening.
    5. Functional System Score (FSS) of > or equal 2 for the pyramidal system or gait impairment due to lower extremity dysfunction
    6. Patients must be between 25 to 55 years of age, inclusive
    7. Women of child-bearing potential must practice an acceptable method of birth control for 30 days before taking the study drug, and 2 acceptable methods of birth control during all study duration and until 30 days after the last dose of treatment is administered.
    8. Patients must sign and date a written informed consent prior to entering the study.
    9. Patients must be willing and able to comply with the protocol requirements for the duration of the study.
    1.I pazienti devono presentare una diagnosi confermata e documentata di SMPP in base alla definizione dei criteri McDonald rivisti del 2010.
    2.Risonanza magnetica per immagini (RMI) al basale che mostri lesioni riferibili a SMPP a livello cerebrale e/o del midollo osseo.
    3.I pazienti devono presentare un punteggio compreso tra 3 e 6,5 (inclusi) nella scala di invalidità espansa (Expanded Disability Status Scale, EDSS) sia alla visita di screening sia alla visita basale.
    4.Evidenza documentata di progressione di invalidità clinica nei 2 anni precedenti lo screening.
    5.Punteggio funzionale di sistema (Functional System Score, FSS) di 2 per il sistema piramidale o disturbo della deambulazione dovuti a una disfunzione degli arti inferiori.
    6.I pazienti devono avere un’età compresa tra i 25 e i 55 anni, inclusi.
    7.Le donne potenzialmente fertili devono utilizzare un metodo accettabile di controllo delle nascite 30 giorni prima di assumere il farmaco in studio e 2 metodi accettabili di controllo delle nascite per tutta la durata dello studio e fino a 30 giorni dopo la somministrazione dell’ultima dose del trattamento.
    8.I pazienti devono firmare e datare un modulo di consenso informato scritto prima di accedere allo studio.
    9.I pazienti devono essere disposti e in grado di attenersi ai requisiti previsti dal protocollo per tutta la durata dello studio.
    E.4Principal exclusion criteria
    1. Patients with history of any multiple sclerosis (MS) exacerbations or relapses, including any episodes of optic neuritis.
    2. Progressive neurological disorder other than PPMS.
    3. Any MRI record showing presence of cervical cord compression.
    4. Baseline MRI showing other findings (including lesions that are atypical for PPMS) that may explain the clinical signs and symptoms.
    5. Relevant history of vitamin B12 deficiency.
    6. Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology.
    7. Use of experimental or investigational drugs in a clinical study within 24 weeks prior to baseline. Use of a currently marketed drug in a clinical study within 24 weeks prior to baseline would not be exclusionary, provided no other exclusion criteria are met.
    8. Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azathioprine
    within 48 weeks prior to baseline.
    9. Previous treatment with fingolimod (GILENYA®, Novartis), dimethyl fumarate (TECFIDERA®, Biogen
    Idec Inc), glatiramer acetate (COPAXONE®, Teva), interferon-β (either 1a or 1b), intravenous
    immunoglobulin, or plasmapheresis within 8 weeks prior to baseline.
    10. Use of teriflunomide (AUBAGIO®, Sanofi) within 2 years prior to baseline, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to baseline.
    11. Prior use of monoclonal antibodies ever, except for:
    a. natalizumab (TYSABRI®, Biogen Idec Inc), if given more than 24 weeks prior to baseline AND the
    patient is John Cunningham (JC) virus antibody test negative (as per medical history)
    b. rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical history) is higher than
    80 cells/μL
    12. Use of mitoxantrone (NOVANTRONE®, Immunex) within 5 years prior to screening. Use of mitoxantrone >5 years before screening is allowed in patients with normal ejection fraction and who did not exceed the total lifetime maximal dose.
    13. Previous use of laquinimod.
    14. Chronic (eg, more than 30 consecutive days or monthly dosing, with the intent of MS disease modification) systemic (intravenous, intramuscular or oral) corticosteroid treatment within 8 weeks prior to baseline.
    15. Previous use of cladribine or alemtuzumab (LEMTRADA®, Sanofi).
    16. Previous total body irradiation or total lymphoid irradiation.
    17. Previous stem cell treatment, cell-based treatment, or bone marrow transplantation of any kind.
    18. Patients who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) within 12 weeks prior to baseline.
    19. Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to baseline.
    20. Use of inducers of CYP3A4 within 2 weeks prior to baseline.
    21. Pregnancy or breastfeeding.
    22. Serum levels ≥3× upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or
    aspartate aminotransferase (AST) at screening.
    23. Serum direct bilirubin which is ≥2×ULN at screening.
    24. Patients with a clinically significant or unstable medical or surgical condition that (in the opinion of the Investigator) would preclude safe and complete study participation, as determined by medical history, physical examinations, electrocardiogram (ECG), laboratory tests or chest X-ray.
    25. A known history of hypersensitivity to gadolinium (Gd).
    26. Glomerular filtration rate (GFR) < or equal 60 mL/min at screening visit.
    27. Inability to successfully undergo MRI scanning, including claustrophobia.
    28. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to mannitol, meglumine or sodium stearyl fumarate.
    1.Pazienti con anamnesi di qualsiasi esacerbazione o recidiva di sclerosi multipla (SM), inclusi eventuali episodi di neurite ottica.
    2.Malattia neurologica progressiva diversa dalla SMPP.
    3.Qualsiasi dato di RMI che mostri la presenza di compressione del midollo spinale a livello cervicale.
    4.RMI al basale che mostri altri risultati (incluse lesioni atipiche per la SMPP) che possano spiegare i segni e sintomi clinici.
    5.Anamnesi relativa a carenza di vitamina B12.
    6.Test sierologico positivo al virus T-linfotropico umano di tipo I e II (HTLV-I/II).
    7.Uso di farmaci sperimentali o in fase di sperimentazione in uno studio clinico nelle 24 settimane prima del basale. L’uso di un farmaco attualmente disponibile in commercio nell’ambito di uno studio clinico nelle 24 settimane prima del basale non determina l’esclusione, sempre che non siano riscontrati altri criteri di esclusione.
    8.Uso di agenti immunosoppressori o citotossici, incluse ciclofosfamide e azatioprina, nelle 48 settimane prima del basale.
    9.Precedente trattamento con fingolimod (GILENYA®, Novartis), dimetilfumarato (TECFIDERA®, Biogen Idec Inc), glatiramer acetato (COPAXONE®, Teva), interferone β (1a o 1b), immunoglobuline per via endovenosa o plasmaferesi nelle 8 settimane prima del basale.
    10.Uso di teriflunomide (AUBAGIO®, Sanofi) nei 2 anni prima del basale, fatta eccezione per il washout attivo (con colestiramina o carbone attivo) eseguito almeno 2 mesi prima del basale.
    11.Pregresso impiego di anticorpi monoclonali, fatta eccezione per:
    a.natalizumab (TYSABRI®, Biogen Idec Inc), se somministrato più di 24 settimane prima del basale E il paziente risulta negativo al test sugli anticorpi del virus di John Cunningham (JC) (in base all’anamnesi)
    b.rituximab, ocrelizumab oppure ofatumumab, se la conta delle cellule B (CD19, in base all’anamnesi) è superiore a 80 cellule/µl
    12.Uso di mitoxantrone (NOVANTRONE®, Immunex) nei 5 anni prima dello screening. L’uso di mitoxantrone più di5 anni prima dello screening è consentito nei pazienti con una normale frazione di eiezione che non hanno superato la dose totale cumulativa massima.
    13.Uso pregresso di laquinimod.
    14.Trattamento con corticosteroidi cronico (ad esempio per più di 30 giorni consecutivi o dosaggio mensile con intenzione di modificare la SM), sistemico (per via endovenosa, intramuscolare oppure orale) nelle 8 settimane prima del basale.
    15.Pregresso uso di cladribina o alemtuzumab (LEMTRADA®, Sanofi).
    16.Pregressa irradiazione totale corporea o irradiazione totale dei linfonodi.
    17.Pregresso trapianto di cellule staminali, trattamento a base di cellule o trapianto di midollo osseo di qualsiasi tipo.
    18.Pazienti sottoposti a trattamento endovascolare per insufficienza venosa cronica cerebrospinale (Chronic Cerebrospinal Venous Insufficiency, CCSVI) nelle 12 settimane prima del basale.
    19.Uso di inibitori moderati/forti del citocromo P450 (cytochrome P450, CYP) 3A4 nelle 2 settimane prima del basale.
    20.Uso di induttori del CYP3A4 nelle 2 settimane prima del basale.
    21.Gravidanza o allattamento.
    22.Livello sierico di alanina aminotransferasi (ALT) o aspartato aminotransferasi (AST) ≥3 volte il limite superiore della norma (Upper Limit of Normal, ULN) allo screening.
    23.Livello sierico della bilirubina diretta ≥2 volte rispetto all’ULN allo screening.
    24.Pazienti con una patologia medica o chirurgica clinicamente significativa o instabile che, a parere dello sperimentatore, precluderebbe una partecipazione sicura e completa allo studio, in base ad anamnesi medica, a esami obiettivi, a elettrocardiogramma (ECG), ad analisi di laboratorio o a radiografia toracica.
    25.Nota anamnesi di ipersensibilità al gadolinio (Gd).
    26.Tasso di filtrazione glomerulare (Glomerular Filtration Rate, GFR) 60 ml/min alla visita di screening.
    27.Incapacità di sottoporsi in modo adeguato alla RMI, inclusa claustrofobia.
    28.Nota ipersensibilità ai farmaci che precluderebbe la somministrazione di laquinimod, come un’ipersensibilità a mannitolo, meglumina o sodio stearil fumarato.
    E.5 End points
    E.5.1Primary end point(s)
    Brain atrophy (BA), defined as change in brain volume
    Atrofia cerebrale (Brain Atrophy, BA), in base alla percentuale di variazione del volume cerebrale (Percentage in Brain Volume Change, PBVC)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Percentage in Brain Volume Change (PBVC) from baseline to week 48
    Atrofia cerebrale (Brain Atrophy, BA), in base alla percentuale di variazione del volume cerebrale (Percentage in Brain Volume Change, PBVC) dal basale alla settimana 48.
    E.5.2Secondary end point(s)
    -Time to CDP (confirmed disability progression) defined by an increase in baseline EDSS
    -Time to CDP defined by an increase in baseline EDSS or at least a 20% worsening in the Timed 25 Foot Walk
    - The number of new T2 brain lesions
    -Change in the BICAMS (Cognitive Assessment for Multiple Sclerosis score)

    •Tempo alla progressione dell’invalidità confermata (Confirmed Disability Progression, CDP), definita come aumento del punteggio EDSS
    •Tempo alla CDP misurata tramite un aumento dal basale nel punteggio EDSS
    •Tempo alla CDP misurata tramite un aumento di almeno il 20% rispetto al basale nel punteggio T25FW
    •Numero di nuove lesioni cerebrali in T2
    •Variazione nel punteggio BICAMS
    E.5.2.1Timepoint(s) of evaluation of this end point
    -Time to confirmed disability progression (CDP), to be confirmed after at least 12 weeks
    -An increase from baseline in EDSS score confirmed after at least 12 weeks
    -An increase of at least 20% from baseline in T25FW score, confirmed after at least 12 weeks
    -The number of new T2 brain lesions at week 48
    -Change from baseline to week 48 in the BICAMS score
    •Tempo alla progressione dell’invalidità confermata (Confirmed Disability Progression, CDP), deve essere confermato dopo almeno 12 settimane.
    •Un aumento dal basale nel punteggio EDSS confermato dopo almeno 12 settimane
    •Un aumento di almeno il 20% rispetto al basale nel punteggio T25FW, confermato dopo almeno 12 settimane
    •Numero di nuove lesioni cerebrali in T2 alla settimana 48
    •Variazione dal basale alla settimana 48 nel punteggio BICAMS
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    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) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA59
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Russian Federation
    Ukraine
    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
    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 months6
    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 months6
    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: 375
    F.1.3Elderly (>=65 years) No
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 211
    F.4.2.2In the whole clinical trial 375
    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)
    Standard of care treatment
    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 Decision2014-12-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-11-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-10-01
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