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    Summary
    EudraCT Number:2015-001870-16
    Sponsor's Protocol Code Number:ISIS396443-CS11
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2021-01-22
    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 number2015-001870-16
    A.3Full title of the trial
    An Open-label Extension Study for Patients with Spinal Muscular Atrophy
    who Previously Participated in Investigational Studies of ISIS 396443
    Studio di estensione in aperto per pazienti con atrofia muscolare spinale che hanno partecipato precedentemente agli studi sperimentali su ISIS 396443
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An extension study for patients with Spinal Muscular Atrophy who
    participated to the previous ISIS 396443 studies
    Studio di estensione per pazienti con atrofia muscolare spinale che hanno partecipato ai precedenti studi ISIS 396443
    A.3.2Name or abbreviated title of the trial where available
    An Open-label Extension Study for Patients with Spinal Muscular Atrophy
    Studio di estensione in aperto per pazienti con atrofia muscolare spinale che hanno partecipato prec
    A.4.1Sponsor's protocol code numberISIS396443-CS11
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02386553
    A.5.4Other Identifiers
    Name:Expanded Access Record Number:NCT02865109
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/251/2016
    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
    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 codeSL64AY
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number00441628501000
    B.5.5Fax number00441628501010
    B.5.6E-mailclinicaltrials@biogen.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 Yes
    D.2.1.1.1Trade name Spinraza
    D.2.1.1.2Name of the Marketing Authorisation holderBiogen Idec Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 namena
    D.3.2Product code [0000]
    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
    D.3.9.3Other descriptive nameISIS 396443
    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
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.3.11.13.1Other medicinal product type2'-MOE Oligonucleotide Antisenso
    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 20.1
    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
    To evaluate the long-term safety and tolerability of nusinersen (ISIS 396443)
    administered by intrathecal (IT) injection to
    subjects with SMA who previously participated in investigational studies of nusinersen.
    Valutare la sicurezza e la tollerabilit¿ a lungo termine di nusinersen (ISIS 396443) somministrato per via intratecale (IT) a pazienti con SMA che hanno partecipato precedentemente a studi sperimentali su nusinersen.
    E.2.2Secondary objectives of the trial
    To examine the long-term efficacy of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to subjects with SMA who previously participated in
    investigational studies of nusinersen.
    Esaminare l'efficacia a lungo termine di nusinersen (ISIS 396443) somministrato per via intratecale (IT) a pazienti con SMA che hanno partecipato precedentemente a studi sperimentali su nusinersen.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must meet all of the following criteria at Screening to be eligible:
    1. Signed informed consent of parent or guardian and signed informed assent of subject, if indicated per subject's age and institutional guidelines
    2. Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks
    Per partecipare allo studio, i soggetti devono soddisfare tutti i seguenti criteri allo screening:
    1. Firma del consenso informato da parte di un genitore o tutore e firma dell'assenso informato del soggetto, se appropriato in base all'età del soggetto e alle linee guida dell'istituto.
    2. Completamento dello studio indice come da protocollo dello studio o in seguito a decisione dello Sponsor (ad esempio, per interruzione anticipata dello studio indice) entro le 16 settimane precedenti.
    E.4Principal exclusion criteria
    Subjects meeting any of the following criteria are not eligible for the study:
    1. Have any condition or worsening condition which in the opinion of the
    Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
    2. Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site
    Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
    3. Partecipant's parent or legal guardian is not willing to meet standard of care guidelines (including vaccinations and respiratory syncytial virus
    prophylaxis if available), nor provide nutritional and respiratory support throughout the study
    4. Treatment with another investigational agent, biological agent, or device within
    one month of Screening, or 5 half-lives of study agent, whichever is longer
    soggetti che soddisfano uno qualsiasi dei seguenti criteri non sono idonei allo studio:
    1. Insorgenza di nuova patologia o peggioramento di patologia esistente che, secondo il parere dello sperimentatore, renderebbe il soggetto non idoneo per l’arruolamento, o potrebbe interferire con la sua capacità di partecipare o portare a termine lo studio.
    2. Anomalie clinicamente significative nei parametri ematologici o ematochimici o nell'elettrocardiogramma (ECG), secondo la valutazione dello sperimentatore del centro, osservate alla visita di Screening, e tali da rendere il soggetto non idoneo a partecipare allo studio..
    3. Incapacità da parte del genitore del partecipante o del tutore del soggetto di comprendere la natura, gli obiettivi e le possibili conseguenze dello studio, oppure incapacità a rispettare il programma di valutazioni previste dal protocollo.
    4. Non disponibilità da parte del genitore o del tutore del soggetto a rispettare le linee guida sullo standard di cura (incluse le vaccinazioni e la profilassi contro il virus respiratorio sinciziale, se disponibile), né a fornire supporto nutrizionale e respiratorio per tutta la durata dello studio.
    E.5 End points
    E.5.1Primary end point(s)
    - Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs)
    - Number of participants with clinically significant vital sign abnormalities
    - Number of participants with clinically significant weight abnormalities
    - Number of participants with clinically significant neurological examination abnormalities
    - Number of participants with clinically significant laboratory assessment abnormalities
    - Number of participants with clinically significant coagulation parameter abnormalities
    - Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
    - Change from Baseline in concomitant medications
    -Numero di partecipanti che sperimentano eventi avversi (AEs) e / o eventi avversi gravi (SAE)
    - Numero di partecipanti con significative anomalie cliniche nei segni vitali
    - Numero di partecipanti con anomalie di peso clinicamente significative
    - Numero di partecipanti con anomalie neurologiche clinicamente significative
    - Numero di partecipanti con anomalie clinicamente significative nei risulati degli esami di laboratorio
    - Numero di partecipanti con anomalie clinicamente significative nei parametri di coagulazione
    - Numero di partecipanti con anomalie clinicamente significative nell' elettrocardiogrammi a 12 derivazioni (ECG)
    - Cambiare da Baseline in farmaci concomitanti
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to Day 1807
    dall'inizio al giorno 1807
    E.5.2Secondary end point(s)
    - Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
    - Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)
    - Time to death or respiratory intervention
    - Percentage of participants not requiring permanent ventilation
    - Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
    - Change from Baseline in Hammersmith Functional Motor Scale
    - Change from Baseline in Revised Upper Limb Module (RULM)
    - Change from Baseline in 6-Minute Walk Test (6MWT)
    - Change from Baseline in Compound Muscular Action Potential (CMAP)
    - Change from Baseline in body length and/or height (for all participants)
    - Change from Baseline in head circumference (for participants up to 36 months of age)
    - Change from Baseline in chest circumference (for participants up to 36 months of age)
    - Change from Baseline in arm circumference (for participants up to 36 months of age)
    - Proportion of CMAP responders
    - Number of participants with motor milestones achieved
    - Proportion of participants who achieved standing alone
    - Proportion of participants who achieved walking with assistance
    - Number of participants with serious respiratory events
    - Number of participants hospitalized
    - Duration of hospitalizations
    - Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine
    - Percentuale di partecipanti che hanno raggiunto le tappe di sviluppo motorio come valutato dai criteri dell'Organizzazione Mondiale della Sanit¿ (OMS)
    - Percentuale di partecipanti che hanno raggiunto le tappe di sviluppo motorio come valutato nella sezione 2 di Hammersmith Infant Neurological Examination (HINE)
    - Periodo di insorgenza di morte o intervento respiratorio
    - Percentuale di partecipanti che non richiedono una ventilazione permanente
    - Scostamento dal Baseline nel Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) nella scala di funzionalit¿ motoria
    - Scostamento dal Baseline nella scala di valutazione motoria funzionale di Hammersmith
    - Scostamento dal baseline nel modulo modificato dell'arto superiore (RULM)
    - Scostamento dal Baseline nel test 6-Minute Walk (6MWT)
    - Scostamento dal baseline della potenza muscolare composta (CMAP)
    - Scostamento dal baseline della lunghezza e / o altezza del corpo (per tutti i partecipanti)
    - Scostamento dal baseline nella circonferenza del capo (per i partecipanti fino a 36 mesi)
    - Scostamento dal baseline nella circonferenza del petto (per i partecipanti fino a 36 mesi)
    - Scostamento dal basale della circonferenza del braccio (per i partecipanti fino a 36 mesi)
    - Proporzione dei rispondenti CMAP
    - Il numero dei partecipanti con tappe di sviluppo motorio raggiunte
    - Proporzione dei partecipanti che sono in grado di stare in piedi da soli
    - Proporzione di partecipanti che sono in grado di stare in piedi assistiti
    - Numero di partecipanti con gravi eventi respiratori
    - Numero di partecipanti ricoverati in ospedale
    - Durata dell'ospedalizzazione
    - Scostamento dal baseline del Cobb-Angles nelle radiografie della colonna toracolombare
    E.5.2.1Timepoint(s) of evaluation of this end point
    Up to Day 1807
    dall'inizio al giorno 1807
    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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open 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 Yes
    E.8.1.7.1Other trial design description
    E' uno studio di estensione in aperto con una fase di caricamento in cieco
    other trial design description (specificare, in inglese): The study is an open label extension
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    na
    na
    E.8.2.4Number of treatment arms in the trial5
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    Hong Kong
    Japan
    Korea, Republic of
    Taiwan
    Turkey
    United States
    Belgium
    France
    Germany
    Italy
    Spain
    Sweden
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    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 years8
    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 Yes
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 50
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 188
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 40
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 14
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    For very young children, parents or legal representative consent will be requested
    Per i bambini molto piccoli, ¿ richiesto il consenso dei genitori o del tutore legale.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 292
    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)
    Patient may be offered the opportunity to continue to receive ISIS 396443. This may occur via early access, extension of the treatment period , enrollment in another open label extension study. Patients may continue to receive treatment via one of these mechanisms until ONE of the following is met: ISIS 396443 is commercially available or is
    rejected in the local country. Sponsor terminates access to ISIS 396443 for reasons including safety issues or emergent data.
    Al pz può essere offerta la pox di continuare a ricevere ISIS 396443. Questo può avvenire tramite accesso precoce, estensione del periodo di trat, arruol in un altro studio di estensione in aperto. I pz pox continuare a ricevere il tratt con uno di questi meccanismi finchè non si verifica una delle seguenti situaz: ISIS 396443 è disp in comm o nn viene autorizzato nel paese. Lo Sponsor potrà porre fine alla fornitura di ISIS 396443 a causa di prob che pox includere la sicurezza o dati emergenti.
    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 Decision2015-12-17
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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