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    Summary
    EudraCT Number:2018-003291-12
    Sponsor's Protocol Code Number:SHP611-201
    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:2020-10-21
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-003291-12
    A.3Full title of the trial
    A Global, Multicenter, Open-label, Matched Historical Control Study of Intrathecal SHP611 in Subjects with Late Infantile Metachromatic Leukodystrophy
    Studio globale, multicentrico, in aperto, abbinato a dati di controllo storici su SHP611 per via intratecale in soggetti affetti da leucodistrofia metacromatica infantile tardiva
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Research study to determine the effects of an investigational drug, SHP611 on patients with with Late Infantile Metachromatic Leukodystrophy (MLD) specially the gross motor function, using the Gross Motor Function
    Classification in Metachromatic Leukodystrophy (GMFC-MLD) compared with matched historical control data in children with MLD.
    Studio di ricerca, per stabilire gli effetti di un farmaco sperimentale, SHP611, su pazienti con leucodistrofia metacromatica (LDM) tardo-infantile, in particolare sulle abilità grosso-motorie, in base alla classificazione delle abilità grosso-motorie nella leucodistrofia metacromatica (Gross Motor Function Classification in Metachromatic Leukodystrophy, [GMFC-MLD]) rispetto ai dati storici di controllo corrispondenti in bambini affetti dalla LDM.
    A.3.2Name or abbreviated title of the trial where available
    ----
    ---
    A.4.1Sponsor's protocol code numberSHP611-201
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN00000000
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03771898
    A.5.3WHO Universal Trial Reference Number (UTRN)U0000-0000-0000
    A.5.4Other Identifiers
    Name:---Number:----
    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 SponsorSHIRE HUMAN GENETIC THERAPIES, INC
    B.1.3.4CountryUnited States
    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 supportShire Human Genetic Therapies, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationShire Human Genetic Therapies, Inc.
    B.5.2Functional name of contact pointDavid Whiteman
    B.5.3 Address:
    B.5.3.1Street Address300 Shire Way
    B.5.3.2Town/ cityLexington
    B.5.3.3Post codeMA 02421
    B.5.3.4CountryUnited States
    B.5.4Telephone number0017814829369
    B.5.5Fax number0017812661365
    B.5.6E-maildavid.whiteman@takeda.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.2.1.1.1Trade name --
    D.2.1.1.2Name of the Marketing Authorisation holder--
    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/3/10/813
    D.3 Description of the IMP
    D.3.1Product name---
    D.3.2Product code [SHP611]
    D.3.4Pharmaceutical form Concentrate for rectal solution
    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 INNRecombinant Human Arylsulfatase A (rhASA)
    D.3.9.2Current sponsor codeSHP611
    D.3.9.3Other descriptive nameRECOMBINANT HUMAN ARYLSULFATASE A
    D.3.9.4EV Substance CodeSUB189761
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Late Metachromatic Leukodystrophy (MLD)
    Leucodistrofia metacromatica (LDM) tardiva
    E.1.1.1Medical condition in easily understood language
    Metachromatic leukodystrophy, the most common form of leukodystrophy, is a rare inherited neurometabolic disorder affecting the white matter of the brain (leukoencephalopathy).
    La leucodistrofia metacromatica, la forma più comune di leucodistrofia, è una rara malattia neurometabolica ereditaria che colpisce la sostanza bianca del cervello (leucoencefalopatia).
    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 10067609
    E.1.2Term Metachromatic leukodystrophy
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic 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 primary objective of this study is to evaluate the effects of intrathecal (IT) administration of SHP611 on gross motor function, using the Gross Motor Function Classification in Metachromatic Leukodystrophy (GMFC-MLD) compared with matched historical control data in children with MLD.If suitable controls cannot be matched despite the sponsor's best efforts, change from baseline results of GMFC-MLD at Week 106 will be compared with a prespecified objective threshold to evaluate primary efficacy for this study.
    L'obiettivo primario del presente studio è valutare gli effetti della somministrazione intratecale (IT) di SHP611 sulla funzione grosso-motoria, mediante la classificazione della funzione grosso-motoria nella leucodistrofia metacromatica (GMFC-MLD) rispetto a dati di controllo storici abbinati nei bambini affetti da MLD. Laddove non sia possibile associare controlli adeguati nonostante il massimo impegno da parte dello sponsor, potrà essere confrontata la variazione dai risultati basali della GMFC-MLD alla settimana 106 con una soglia obiettivo prestabilita per valutare l'efficacia primaria del presente studio.
    E.2.2Secondary objectives of the trial
    - To evaluate the effects of IT administration of SHP611 on gross motor function, using the Gross Motor Function Measure 88 (GMFM-88) total score in children with MLD
    - To evaluate the effects of IT administration of SHP611 on the time course of declining gross motor functionusing GMFC-MLD
    - To evaluate the effects of IT administration of SHP611 on the time course of declining gross motor function using GMFM-88
    - To evaluate the effects of IT administration of SHP611 on expressive language using the Expressive Language Function Classification (ELFCMLD)
    - To evaluate the effects of IT administration of SHP611 on cerebrospinal fluid (CSF) biomarker (ie, sulfatides)
    - To evaluate the effects of IT administration of SHP611 on proton magnetic resonance spectroscopy (MRS) of the brain, specifically Nacetylaspartate/Creatine (NAA/Cr) in white matter
    - To evaluate the effects of IT administration of SHP611 on Eichler MLD MRI severity score
    •Valutare effetti somministrazione IT di SHP611 sulla funzione grosso-motoria, mediante punteggio complessivo del Gross Motor Function Measure 88 (GMFM-88) nei bambini affetti da MLD • Effetti somministrazione IT di SHP611 sull'andamento temporale del declino della funzione grosso-motoria mediante la GMFC-MLD .• Effetti somministrazione IT di SHP611 sull'andamento temporale del declino della funzione grosso-motoria mediante il GMFM-88 •Effetti somministrazione IT di SHP611 sul linguaggio espressivo mediante scala Expressive Language Function Classification (ELFC-MLD) •Effetti somministrazione IT di SHP611 sul biomarcatore del liquido cerebrospinale (CSF) (ovvero, solfatidi) • Effetti somministrazione IT di SHP611 nella spettroscopia protonica con risonanza magnetica (MRS) del cervello, in particolare i livelli di N-Acetil-Aspartato/Creatina (NAA/Cr) nella materia bianca •Valutare effetti somministrazione IT di SHP611 mediante punteggio Eichler di gravità della MLD secondo RM
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    FOR COMPLETE LIST REFER TO PROTOCOL
    Patients must meet all of the following criteria to be considered eligible for inclusion as a subject
    in the study:
    1. The subject must have a documented diagnosis of MLD (Groups A-E)
    a. Low ASA activity in leukocytes (compared to laboratory normal range)
    AND
    b. Elevated sulfatides in urine
    2. The subject must have a gait disorder due to spastic ataxia or weakness attributed to MLD by the investigator
    and documented by a pediatric neurologist or medical geneticist by 30 months of age (Groups A-C, and F), or
    be minimally symptomatic and =6 to <18 months of age (Group D), or be early symptomatic and =12 to <18
    months of age (Group E). Subjects in Group E must have neurological symptoms documented by a pediatric
    neurologist or medical geneticist.
    3. The subject’s age at the time of informed consent, must be:
    ¿ Group A: 18 to 48 months of age
    ¿ Group B: 18 to 72 months of age
    ¿ Group C: 18 to 72 months of age
    ¿ Group D: =6 to <18 months of age
    ¿ Group E: =12 to <18 months of age
    ¿ Group F: 18 to 72 months of age
    4. The subject’s GMFC-MLD level at screening must be:
    ¿ Group A: GMFC-MLD level of 1 or 2
    ¿ Group B: GMFC-MLD level of 3
    ¿ Group C: GMFC-MLD level of 4
    ¿ Group D: minimally symptomatic; younger siblings of enrolled subjects, and have the same ASA
    allelic constitution
    ¿ Group E: GMFC-MLD level of 1 or 2 with a history of achieving stable walking (defined as at least 1
    month of independent walking)
    ¿ Group F: GMFC-MLD level of 5 or 6
    5. The subject and his/her parent/representative(s) must have the ability to comply with the clinical protocol
    6. Subject's parent or legally authorized representative(s) must provide written informed consent prior to
    performing any study-related activities. Study-related activities are any procedures that would not have been
    performed during normal management of the subject
    Inclusion criteria for matched historical controls: Subjects must meet all of the following criteria to be
    considered eligible for inclusion as a matched historical control:
    1. The subject must have a documented diagnosis of MLD
    a. Low ASA activity in leukocytes (compared to laboratory normal range)
    AND
    b. Elevated sulfatides in urine
    Subjects must have a gait disorder due to spastic ataxia or weakness attributed to MLD by the investigator
    and documented by 30 months of age
    3. Subjects must have at least 2 motor assessments by GMFC-MLD with the second assessment occurring at
    approximately 106 (±2) weeks after the first assessment or else a second assessment measured before
    Week 100 with a GMFC-MLD level 5 or 6. Subjects with GMFC-MLD data (pro or retrospectively
    determined) must have the earliest observation of 1 or 2 (walking with support) in the data source-verified
    medical record
    4. Subjects must be 18 to 48 months of age at the earliest assessment
    PER LISTA COMPLETA FARE RIFERIMENTO AL PROTOCOLLO
    I pazienti devono soddisfare tutti i seguenti criteri per essere considerati idonei ad essere inclusi come soggetti partecipanti allo studio:
    1. Il soggetto deve avere una diagnosi documentata di MLD (Gruppi A-E)
    a. Bassa attività ASA nei leucociti (rispetto all’intervallo normale di laboratorio)
    E
    b. Solfati elevati nelle urine
    2. Il soggetto deve manifestare un disturbo della deambulazione dovuto ad atassia spastica o debolezza attribuita alla MLD dallo sperimentatore, documentato da un neurologo pediatrico o da un medico genetista entro i 30 mesi di età (Gruppi A-C, e F), o essere minimamente sintomatico e di età da =6 a <18 mesi (Gruppo D), o avere sintomi precoci e un’età da =12 a <18 mesi (Gruppo E). I soggetti del Gruppo E devono avere sintomi neurologici documentati da un neurologo pediatrico o da un medico genetista.
    3. L'età del soggetto al momento del consenso informato, deve essere:
    • Gruppo A: da 18 a 48 mesi
    • Gruppo B: da 18 a 72 mesi
    • Gruppo C: da 18 a 72 mesi
    • Gruppo D: da =6 a <18 mesi
    • Gruppo E: da =12 a <18 mesi
    • Gruppo F: da 18 a 72 mesi
    4. Il livello GMFC-MLD del soggetto al momento dello screening deve essere:
    • Gruppo A: livello 1 o 2 GMFC-MLD
    • Gruppo B: livello 3 GMFC-MLD
    • Gruppo C: livello 4 GMFC-MLD
    • Gruppo D: minimamente sintomatici; fratelli minori dei soggetti arruolati e stessa costituzione allelica ASA
    • Gruppo E: livello 1 o 2 GMFC-MLD con anamnesi di comprovata deambulazione stabile (definita come almeno 1 mese di deambulazione indipendente)
    • Gruppo F: livello 5 o 6 GMFC-MLD
    5. Il soggetto e il suo genitore/rappresentante/ devono essere in grado di rispettare il protocollo clinico
    6. I genitori o i rappresentante/i legalmente autorizzato/i del soggetto devono fornire il consenso informato per iscritto prima di eseguire qualsiasi attività correlata allo studio. Le attività correlate allo studio sono tutte le procedure che non sarebbero state eseguite durante la normale gestione del soggetto
    Criteri di inclusione per il gruppo di controllo storico abbinato: I soggetti devono soddisfare tutti i seguenti criteri per essere considerati idonei ad essere inclusi nel gruppo di controllo storico abbinato:
    1. Il soggetto deve avere una diagnosi documentata di MLD
    a. Bassa attività ASA nei leucociti (rispetto all’intervallo normale di laboratorio)
    E
    b. Solfati elevate nelle urine
    2. I soggetti devono manifestare un disturbo della deambulazione dovuto ad atassia spastica o debolezza attribuita alla MLD dallo sperimentatore, documentato entro i 30 mesi di età
    3. I soggetti devono aver ricevuto almeno 2 valutazioni motorie mediante GMFC-MLD e la seconda valutazione deve avvenire a circa 106 (±2) settimane dopo la prima valutazione o una seconda valutazione deve essere misurata prima della settimana 100 con un GMFC-MLD di livello 5 o 6. I soggetti con dati GMFC-MLD (determinati prospettivamente o retrospettivamente) devono aver ricevuto la prima osservazione di 1 o 2 (camminare con il supporto nei dati sorgente verificati nella cartella clinica.
    4. I soggetti devono avere un’età compresa tra 18 e 48 mesi alla prima valutazione
    E.4Principal exclusion criteria
    FOR COMPLETE LIST REFER TO PROTOCOL
    Multiple sulfatase disorder as determined by abnormal activity of another lysosomal sulfatase (based upon the
    reference laboratory’s normal range) or a known genetic disorder other than MLD
    2. History of bone marrow transplant (BMT), hematopoietic stem cell transplantation (HSCT), or gene therapy
    or undergoes BMT, HSCT, or gene therapy at any point during the study
    3. Primary presentation of MLD was behavioral or cognitive symptoms (per investigator’s clinical judgment);
    behavioral symptoms that are secondary to motor deficits (eg: tantrums in response to loss of motor skills) are
    not exclusionary.
    4. The subject has any known or suspected hypersensitivity to agents used for anesthesia or has history of
    difficult airway or potential for airway compromise
    5. Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude
    participation in the study
    6. Subjects with laboratory, ECG or vital sign abnormalities reflecting intercurrent illness that may compromise
    their safety during the trial should not be enrolled. Abnormal laboratory, vital sign and ECG results at
    screening should be reviewed with the Shire medical monitor.
    7. The subject is enrolled in another clinical study that involves use of any investigational product (drug or
    device) within 30 days or 5 half-lives (whichever is longer) prior to study enrollment or at any time during the
    study
    8. The subject has a condition that is contraindicated as described in the SOPH-A-PORT Mini S IDDD
    Instructions for Use
    a. The patient has had, or may have, an allergic reaction to the materials of construction
    b. The patient has shown an intolerance to an implanted device
    c. The patient’s body size is too small to support the size of the SOPH-A-PORT Mini S Access Port
    d. The patient’s drug therapy requires substances known to be incompatible with the materials of
    construction
    e. The patient has a known or suspected local or general infection
    f. The patient is at risk of abnormal bleeding due to a medical condition or therapy
    g. The patient has one or more spinal abnormalities that could complicate safe implantation or fixation
    h. The patient has a functioning CSF shunt device
    Exclusion criteria for matched historical controls:
    1. History of bone marrow transplant (BMT), hematopoietic stem cell transplantation (HSCT), or gene therapy
    or undergoes BMT, HSCT, or gene therapy at any point during the study
    2. Primary presentation of MLD was behavioral or cognitive symptoms (per investigator’s clinical judgment);
    behavioral symptoms that are secondary to motor deficits (eg; tantrums in response to loss of motor skills) are
    not exclusionary.
    3. The subject is enrolled in another clinical study that involves use of any investigational product (drug or
    device)
    PER LISTA COMPLETA FARE RIFERIMENTO AL PROTOCOLLO
    1. Malattia da deficienza multipla di solfatasi determinata da un’attività anomala di una diversa solfatasi lisosomiale (in base all’intervallo normale del laboratorio di riferimento) o disturbo genetico noto diverso dalla MLD
    2. Anamnesi di trapianto di midollo osseo (BMT), trapianto di cellule staminali ematopoietiche (HSCT) o terapia genica oppure doversi sottoporre a BMT, HSCT o terapia genica in qualsiasi momento dello studio
    3. La manifestazione primaria della MLD erano sintomi comportamentali o cognitivi (in base al giudizio clinico dello sperimentatore); i sintomi comportamentali secondari ai deficit motori (ad esempio: capricci in risposta alla perdita delle capacità motorie) non sono escludenti
    4. Il soggetto presenta una qualsiasi ipersensibilità nota o sospetta agli agenti utilizzati per l'anestesia o un’anamnesi di vie respiratorie complesse o una possibile compromissione delle vie respiratorie
    5. Qualsiasi altra condizione medica o comorbilità grave che, secondo l'opinione dello sperimentatore, precluderebbe la partecipazione allo studio
    6. I soggetti che presentano anomalie nei dati di laboratorio, ECG o parametri vitali che riflettono malattie intercorrenti che possono comprometterne la sicurezza durante la sperimentazione non devono essere arruolati. I risultati anomali dei dati di laboratorio, dei parametri vitali e dei risultati dell'ECG al momento dello screening devono essere esaminati con il medical monitor di Shire.
    7. Il soggetto è arruolato in un altro studio clinico che prevede l'uso di qualsiasi prodotto sperimentale (farmaco o dispositivo) entro 30 giorni o 5 emivite (a seconda di quale sia il periodo più lungo) prima dell'arruolamento nello studio o in qualsiasi momento durante lo studio.
    8. Il soggetto presenta una condizione controindicata come descritto nel manuale di Istruzioni per l'uso dell’IDDD SOPH-A-PORT Mini S
    a. Il paziente ha avuto o potrebbe avere una reazione allergica ai materiali di fabbricazione
    b. Il paziente ha mostrato un'intolleranza a un dispositivo impiantato
    c. La corporatura del paziente è troppo ridotta per supportare le dimensioni della porta di accesso del dispositivo SOPH-A-PORT Mini S
    d. La terapia farmacologica del paziente richiede sostanze note per essere incompatibili con i materiali di fabbricazione
    e. Il paziente ha un'infezione locale o generale nota o sospetta
    f. Il paziente è a rischio di emorragia anomala a causa di una condizione medica o terapia
    g. Il paziente presenta una o più anomalie spinali che potrebbero complicare un impianto o una fissazione sicuri
    h. Il paziente ha un dispositivo di shunt funzionante per il CSF
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is response in Group A, defined as
    maintenance of gross motor function at 2 years (Week 106), evaluated
    as no greater than 2 levels decline from baseline in GMFC-MLD.
    If suitable controls cannot be matched despite the sponsor's best efforts,
    change from baseline results of GMFC-MLD at Week 106 will be
    compared with a prespecified objective threshold to evaluate primary
    efficacy for this study.
    L'endpoint di efficacia primario è la risposta nel gruppo A, definita come mantenimento della funzione grosso-motoria a 2 anni (Settimana 106), valutato come declino non superiore a 2 livelli rispetto al basale nel GMFC-MLD.
    Laddove non sia possibile abbinare dati del gruppo di controllo adeguati nonostante il massimo impegno da parte dello sponsor, la variazione dai risultati basali del GMFC-MLD alla Settimana 106 può essere confrontata con una soglia obiettivo prestabilita per valutare l'efficacia primaria per questo studio.
    E.5.1.1Timepoint(s) of evaluation of this end point
    2 years (week 106)
    2 anni (Settimana 106)
    E.5.2Secondary end point(s)
    - Response in Group A, defined as maintenance of gross motor function
    at 2 years (Week 106), defined as a GMFM-88 total score >40
    - Change from baseline at Week 106 of gross motor function, using the
    GMFC-MLD
    - Change from baseline at Week 106 of gross motor function, using the
    GMFM-88 total score GMFM-88 total score decline of no more than 20
    points from baseline and a total score that is =40 at Week 106
    - Time to unreversed decline from baseline in GMFC-MLD of more than 2
    categories, defined as any decline of more than 2-categories that has not
    reverted to a 2-category decline (or better) as of the last recorded
    observation
    - Time to unreversed decline from baseline in GMFM-88 total score of
    >20 points or unreversed decline to <40 points, whichever occurs first
    - Change from baseline at Week 106 in expressive language using the
    ELFC-MLD
    - Change from baseline at Week 106 in CSF sulfatides levels
    - Change from baseline at Week 106 in MRS metabolite levels,
    specifically: N-acetylaspartate/Creatine
    - Change from baseline at Week 106 in Eichler MLD MRI severity score
    • Risposta nel Gruppo A, definita come mantenimento della funzione grosso-motoria a 2 anni (Settimana 106), definita come punteggio complessivo del GMFM-88 >40
    • Variazione rispetto al basale alla Settimana 106 della funzione grosso-motoria, mediante la GMFC-MLD
    • Variazione rispetto al basale alla Settimana 106 della funzione grosso-motoria, mediante il punteggio complessivo del GMFM-88
    • Peggioramento non superiore a 20 punti del punteggio complessivo del GMFM-88 rispetto al basale e punteggio complessivo =40 alla Settimana 106
    • Tempo fino al declino non reversibile rispetto al basale in GMFC-MLD superiore a 2 categorie, definito come qualsiasi declino superiore a 2 categorie che non sia ritornato a un declino di 2 categorie (o migliore) a partire dall'ultima osservazione registrata
    • Tempo fino al declino non reversibile rispetto al basale in punteggio totale GMFM-88 >20 punti o declino non reversibile <40 punti, a seconda di quale si verifica per primo
    • Variazione rispetto al basale alla Settimana 106 nel linguaggio espressivo mediante la ELFC-MLD
    • Variazione rispetto al basale alla Settimana 106 nei livelli dei sulfatidi del CSF
    • Variazione rispetto al basale alla Settimana 106 nei livelli dei metaboliti MRS, in particolare i livelli di N-Acetil-Aspartato/Creatina
    • Variazione rispetto al basale alla Settimana 106 nel punteggio punteggio Eichler di gravità della MLD secondo RM
    E.5.2.1Timepoint(s) of evaluation of this end point
    2 years
    2 anni
    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 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) 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 No
    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
    in aperto
    open
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    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
    Belgium
    Brazil
    Canada
    France
    Germany
    Israel
    Japan
    Netherlands
    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
    The Study Completion Date is defined as the date on which the last subject in the study completes the final protocol-defined assessment(s). This includes the follow-up visit or contact, whichever is later.
    La Data di conclusione dello studio è definita come la data in cui l'ultimo soggetto nello studio completa le valutazioni definitive definite dal protocollo. Ciò include la visita di follow-up o il contatto, a seconda di quale si verifichi più tardi
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days15
    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: 12
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 30
    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.3.3.6.1Details of subjects incapable of giving consent
    Children up to 72 months
    Bambini fino a 72 mesi
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 11
    F.4.2.2In the whole clinical trial 42
    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)
    Subjects who complete the study will be offered the opportunity to
    continue in a separate extension study (SHP611-202), provided that
    they meet the study eligibility criteria, where they may continue to
    receive treatment with SHP611 for an extended duration of time.
    For subjects who elect to discontinue the study, a safety follow-up visit
    will be conducted at Week 108 and the IDDD will be removed upon
    discontinuation from the study.
    Per i soggetti che scelgono di interrompere lo studio, sarà condotta una visita di follow-up di sicurezza alla Settimana 108 e il dispositivo per la somministrazione intratecale di farmaci (Intrathecal Drug Delivery Device, [IDDD]) verrà rimosso in seguito a interruzione della partecipazione allo studio.
    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 Decision2020-10-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-09-09
    P. End of Trial
    P.End of Trial StatusOngoing
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