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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43206   clinical trials with a EudraCT protocol, of which   7151   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2014-002098-12
    Sponsor's Protocol Code Number:232SM201
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-03-24
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-002098-12
    A.3Full title of the trial
    An Open-Label Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Subjects With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
    Studio in aperto volto alla valutazione dell’efficacia, la sicurezza, la tollerabilità e la farmacocinetica di ISIS 396443 somministrato in dosi multiple per via intratecale in soggetti con diagnosi genetica di atrofia muscolare spinale in fase presintomatica.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Multiple Doses of ISIS ISIS 396443 Delivered to Infants with
    Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
    Uno studio di dosi multiple di ISIS 396443 somministrato a neonati con atrofia muscolare spinale in fase presintomatica geneticamente diagnosticata
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code number232SM201
    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 SponsorBiogen Idec Research Limited
    B.1.3.4CountryUnited Kingdom
    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 supportBiogen Idec Research Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBiogen Idec
    B.5.2Functional name of contact pointMedical Director
    B.5.3 Address:
    B.5.3.1Street AddressInnovation House, 70 Norden Road
    B.5.3.2Town/ cityMaidenhead
    B.5.3.3Post codeSL6 4AY
    B.5.3.4CountryUnited Kingdom
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/12/976
    D.3 Description of the IMP
    D.3.1Product nameSurvival of Motor Neuron 2 (SMN2) Splicing Modulator Antisense Oligonucleotide
    D.3.2Product code ISIS 396443 (BIIB058)
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntrathecal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNISIS 396443
    D.3.9.1CAS number 1258984-36-9
    D.3.9.2Current sponsor codeISIS 396443 (BIIB058)
    D.3.9.3Other descriptive nameISIS 396443 (BIIB058)
    D.3.9.4EV Substance CodeSUB130563
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.4
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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 Yes
    D. medicinal product type2 - MOE Antisense Oligonucleotide
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Spinal Muscular Atrophy (SMA)
    Atrofia Muscolare Spinale (SMA)
    E.1.1.1Medical condition in easily understood language
    Spinal Muscular Atrophy (SMA)
    Atrofia Muscolare Spinale (SMA)
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10041582
    E.1.2Term Spinal muscular atrophy
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to examine the efficacy of multiple doses of ISIS 396443 administered intrathecally in preventing or delaying the need for respiratory intervention or death in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA).
    L’obiettivo primario dello studio è quello di esaminare l’efficacia di ISIS 396443 somministrato in dosi multiple per via intratecale nel prevenire o ritardare il bisogno di intervento respiratorio o decesso nei bambini con diagnosi genetica di SMA in fase presintomatica
    E.2.2Secondary objectives of the trial
    Secondary objectives of this study are to examine the effects of ISIS 396443 in infants with genetically diagnosed and presymptomatic SMA.
    Gli obiettivi secondari di questo studio sono quelli di esaminare gli effetti di ISIS 396443 nei bambini con diagnosi genetica di SMA presintomatica
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Age ≤ 6 weeks at first dose
    - Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound heterozygous mutation.
    - Genetic documentation of 2 or 3 copies of survival motor neuron 2 (SMN2).
    - Compound muscle action potential (CMAP) ≥ 1 mV at Baseline.
    - Gestational age of 37 to 42 weeks for singleton births; gestational age of 34 to 42 weeks for twins.
    - Meet additional study related criteria.
    - età ≤6 settimane alla prima dose
    - documentazione genetica di mutazione o delezione omozigote del gene 5q della SMA o mutazione eterozigote composto
    - documentazione genetica di 2 o 3 copie del gene di sopravvivenza dei motoneuroni 2(SMN2)
    -Potenziale di azione muscolare compopsto (CMAP) ≥1 mV al Basale
    - Età gestazionale da 37 a 42 settimane per le nascite di neonato unico; età gestazionale
    di 34 a 42 settimane per i gemelli
    - Soddisfare i criteri addizionali relativi allo studio.
    E.4Principal exclusion criteria
    - Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support).
    - Any clinical signs or symptoms at Screening or immediately prior to dosing that are, in the opinion of the Investigator, strongly suggestive of SMA.
    - Clinically significant abnormalities in hematology or clinical chemistry parameters.
    - Treatment with an investigational drug given for the treatment of SMA biological agent, or device. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation.
    - Meet additional study related criteria.
    E.4 Criteri di esclusione principali(elencare i più importanti):
    - Ipossiemia (saturazione di ossigeno <96% sveglio o addormentato senza
    ossigeno supplementare o supporto respiratorio).
    - Eventuali segni o sintomi clinici allo screening o immediatamente prima
    della somministrazione della dose che sono, a giudizio dello sperimentatore, fortemente suggestivi di SMA.
    - Alterazioni clinicamente significative nei parametri di ematologia o chimica clinica
    - Il trattamento con un farmaco sperimentale proposta per il trattamento della SMA,
    agente biologico, o dispositivo. Ogni storia di terapia genica, precedente trattamento con oligonucleotide antisenso (ASO) trattamento, o trapianto di cellule.
    - Soddisfare i criteri addizionali relativi allo studio.
    E.5 End points
    E.5.1Primary end point(s)
    Time to death or respiratory intervention. The time will be the age of the participant at the first occurrence of either a respiratory intervention or death. Respiratory intervention is defined as invasive or noninvasive ventilation for ≥6 hours/day continuously for 7 or more days OR tracheostomy.
    Tempo al decesso o all’intervento respiratorio. Il tempo sarà l’età del soggetto alla prima ricorrenza di intervento respiratorio o di decesso. L’intervento respiratorio è definito come ventilazione invasiva o non invasiva per ≥6 ore/giorno in modo continuativo per 7 giorni o più O tracheostomia.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to Day 868
    Fino al giorno 868
    E.5.2Secondary end point(s)
    1 Percentage of participants developing clinically manifested spinal muscular trophy(SMA)
    2 Percentage of participants alive
    3 Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE)
    4 Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
    5 Change from Baseline in the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
    6 Change from Baseline in weight for age/length
    7 Change from Baseline in head chest and arm circumference
    8 Change from Baseline in head to chest circumference ratio
    9 Incidence of adverse events (AEs) and/or serious adverse events (SAEs).
    10 Change from Baseline in clinical laboratory parameters, electrocardiograms (ECGs), and vital signs
    11 Cerebrospinal fluid (CSF) and plasma ISIS 396443 concentrations
    1. Percentuale di soggetti che sviluppano una atrofia muscolare spinale (SMA) clinicamente manifestata
    2. Percentuale di soggetti vivi
    3. Percentuale di soggetti che hanno raggiunto acquisizioni motorie secondo i criteri dell’HINE (Hammersmith Infant Neurological Examination)
    4. Verrà presentata la proporzione di soggetti che hanno raggiunto acquisizioni motorie secondo i criteri dell’OMS
    5. I cambiamenti dal valore basale nei parametri della scala di valutazione della funzionalità motoria Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).

    6. Variazione rispetto al basale nel peso/ lunghezza per età
    7. Variazione rispetto al basale nella circonferenza della testa, del petto e del braccio
    8. Cambiamento dal basale nel rapporto di circonferenza testa/torace
    9. L'incidenza di eventi avversi (EA) e / o eventi avversi gravi
    10. Variazione rispetto al basale dei parametri clinici di laboratorio,
    elettrocardiogramma (ECG), e segni vitali
    11. Concentrazioni di ISIS 396.443 nel liquido cerebrospinale (CSF) e plasma
    E.5.2.1Timepoint(s) of evaluation of this end point
    Points 1-8 inclusive will be measured at 13 and 24 months of age
    Points 9 and 10 inclusive will be measured up to 868 days
    Point 11 will be measured up to 778 days
    I punti dall’1-8 inclusi saranno misurati a 13 e 24 mesi di età
    I punti 9 e 10 inclusi verranno misurati fino a 868 giorni
    Il punto 11 sarà misurato fino a 778 giorni
    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 No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity assessments
    Valutazioni di immunogenicità
    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. 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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months11
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 25
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
    F. of subjects for this age range: 2
    F.1.1.3Newborns (0-27 days) Yes
    F. of subjects for this age range: 17
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F. of subjects for this age range: 6
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    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 No
    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 Yes
    F. of subjects incapable of giving consent
    The trial will enrol babies 6 weeks old or less who are unable to provide
    informed consent. Before a subject's participation in the trial, the
    Investigator will be required to obtain written informed consent from
    the parent(s) or legal guardian(s)
    Verranno arruolati bambini con meno di 6 settimane di vita, non in grado di fornire il consenso informato. Prima della partecipazione di un soggetto,lo Sperimentatore dovrà ottenere il consenso informato scritto dai genitori o dai tutorei legali
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 6
    F.4.2.2In the whole clinical trial 25
    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)
    Please see protocol section 11.6
    Si prega di fare riferimento al protocollo, sezione 11.6
    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 Decision2015-05-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-04-01
    P. End of Trial
    P.End of Trial StatusOngoing
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