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    Summary
    EudraCT Number:2021-002480-22
    Sponsor's Protocol Code Number:TAK-935-3001
    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:2021-07-27
    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 number2021-002480-22
    A.3Full title of the trial
    A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Soticlestat as Adjunctive Therapy in Pediatric and Young Adult Subjects With Dravet Syndrome (DS)
    Studio multicentrico, randomizzato, in doppio cieco, controllato con placebo, a gruppi paralleli per valutare l’efficacia, la sicurezza e la tollerabilità di soticlestat come terapia aggiuntiva in soggetti pediatrici e giovani adulti affetti da sindrome di Dravet (SD)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of Soticlestat as Adjunctive Therapy in Pediatric and Young Adult Subjects With Dravet Syndrome
    Studio su Soticlestat come terapia aggiuntiva in soggetti pediatrici e giovani adulti affetti da sindrome di Dravet
    A.3.2Name or abbreviated title of the trial where available
    Skyline
    Skyline
    A.4.1Sponsor's protocol code numberTAK-935-3001
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/317/2020
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorTAKEDA DEVELOPMENT CENTER AMERICAS 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 supportTakeda Development Center Americas, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTakeda Development Center Americas, Inc.
    B.5.2Functional name of contact pointMedical Director
    B.5.3 Address:
    B.5.3.1Street Address95 Hayden Avenue
    B.5.3.2Town/ cityLexington, MA
    B.5.3.3Post code02421
    B.5.3.4CountryUnited States
    B.5.4Telephone number0016174441422
    B.5.5Fax number0000000
    B.5.6E-mailDimitrios.Arkilo@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.2.5The 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 nameSoticlestat
    D.3.2Product code [TAK-935]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPGastroenteral use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNsoticlestat
    D.3.9.1CAS number 1429505-03-2
    D.3.9.2Current sponsor codeTAK-935
    D.3.9.4EV Substance CodeSUB198078
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 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 namesoticlestat
    D.3.2Product code [TAK-935]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPGastroenteral use
    Oral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNsoticlestat
    D.3.9.1CAS number 1429505-03-2
    D.3.9.2Current sponsor codeTAK-935
    D.3.9.4EV Substance CodeSUB198078
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Dravet Syndrome (DS)
    Sindrome di Dravet (SD)
    E.1.1.1Medical condition in easily understood language
    Seizures
    Convulsioni
    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 LLT
    E.1.2Classification code 10073682
    E.1.2Term Dravet syndrome
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To assess the efficacy of soticlestat in reducing convulsive seizure frequency as add-on therapy to SOC as compared with placebo during the full treatment period (titration + maintenance).

    - To assess the efficacy of soticlestat in reducing convulsive seizure frequency as add-on therapy to SOC compared with placebo during the maintenance period only.
    - Valutare l'efficacia di soticlestat nel ridurre la frequenza delle crisi epilettiche come terapia aggiuntiva al SOC rispetto al placebo durante l'intero periodo di trattamento (titolazione + mantenimento).

    - Valutare l'efficacia di soticlestat nel ridurre la frequenza delle crisi epilettiche come terapia aggiuntiva al SOC rispetto al placebo durante il solo periodo di mantenimento.
    E.2.2Secondary objectives of the trial
    To assess the following in subjects taking soticlestat as compared with placebo during the full treatment period, unless otherwise noted:
    - Proportion of treatment responders defined as those with =50% reduction in convulsive seizures from baseline during the maintenance period and the full treatment period.
    - Effect on total seizure frequency of all seizure types during the maintenance period and the full treatment period.
    - Change from baseline in proportion of convulsive seizure-free days.
    - Longest convulsive seizure-free interval.
    - Number of days when rescue antiseizure medications (ASMs) are used.
    - Effect on the Clinical Global Impression of Improvement (CGI-I) (clinician) and Caregiver Global Impression of Improvement (Care GI-I).
    - Effect on CGI-I Seizure Intensity and Duration.
    - Effect on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregivers.
    - Effect on Quality of Life Inventory-Disability (QI-Disability).
    Valutare quanto segue nei soggetti che assumono soticlestat rispetto al placebo durante l'intero periodo di trattamento, salvo diversa indicazione:
    - Percentuale di soggetti che rispondono al trattamento, definiti come coloro che hanno con una riduzione =50% delle crisi epilettiche dal basale durante il periodo di mantenimento e l'intero periodo di trattamento.
    - Effetto sulla frequenza totale delle crisi di tutti i tipi di crisi durante il periodo di mantenimento e l'intero periodo di trattamento.
    - Variazione rispetto al basale nella percentuale di giorni senza crisi epilettiche.
    - L'intervallo di tempo più lungo senza crisi epilettiche.
    - Numero di giorni in cui vengono utilizzati farmaci ASM.
    - Effetto sulla CGI-I (clinico) e Care GI-I (caregiver)
    - Effetto sul CGI-I relativo all’intensità e sulla durata delle crisi.
    - Effetto sul CGI-I relativo ai sintomi non convulsivi completato dal clinico con il contributo dei caregiver.
    - Effetto sul QI-Disabilità
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. In the opinion of the investigator, the subject and/or parent or legal guardian is capable of understanding and complying with protocol requirements including the use of digital tools, complete appropriate assessments, maintain an accurate and complete daily seizure diary and take study drug for the duration of the study.
    2. The subject or the subject’s parent or legal guardian are willing and able to read, understand, and sign and date a written or an electronic informed consent form (ICF), assent form (if applicable), and any required privacy authorization prior to the initiation of any study procedures.
    3. The subject is male or female and aged 2 to 21 years, inclusive, at the time of informed consent.
    4. Documented clinical diagnosis of DS supported by:
    - Onset of seizures usually in the first year of life.
    - History of fever-induced prolonged seizure as determined by the investigator:
    - May include prolonged (approximately 15 minutes or longer) hemi-clonic seizures.
    - Multiple seizure types, which may include:
    – Generalized tonic-clonic.
    – Focal to bilateral tonic-clonic.
    - Clonic.
    – Myoclonic seizures.
    - History of developmental delay/intellectual disability presenting after onset of seizures and usually presenting after 12 months of age.
    - Documented genetic mutation consistent with DS is not required, but results of genetic testing will be collected if available. If genetic testing was not performed previously or if the SCN1A result is negative (without any other positive gene reported that is consistent clinically with DS), testing for SCN1A will be offered at the time of screening.
    5.Has =4 convulsive seizures in each 1-month period in the 3 months before screening based on the historical information and has =4 convulsive seizures per 28 days during the 4- to 6- week prospective baseline period.
    6. Weighs =10 kg at the screening visit (Visit 1).
    7. Failure to control seizures despite appropriate trials of at least 2 ASMs based on historical information and is currently on an antiseizure therapy (eg ASMs, vagus nerve stimulation (VNS), ketogenic/modified Atkins diet) or other treatment options considered as SOC.
    8. Currently taking 0 to 4 ASMs at stable doses for at least 4 weeks before the screening visit (Visit 1); benzodiazepines used chronically (daily) to treat seizures are considered ASMs. ASM dosing regimen must remain constant throughout the study.
    9. If using a VNS, the subject must have had VNS placed at least 3 months before the screening visit with stable settings for >1 month; VNS parameters must remain constant throughout the study (VNS will not be counted as an ASM).
    10. If on ketogenic diet (or any other diet used for treatment of epilepsy, such as modified Atkins diet), the subject must have started the diet at least 3 months before the screening visit (Visit 1), and the subject’s diet should be stable for 1 month before the screening visit (Visit 1); the subject should continue this diet throughout the duration of the study (ketogenic diet, or any other diet for the treatment of epilepsy will not be counted as an ASM).
    11. The use of felbamate is allowed provided that the subject does not meet the liver function test (LFT) exclusion criteria, the dose has been stable for at least 6 months before screening, and the subject has had stable liver function (as determined by serum aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels) and hematology laboratory tests during the course of treatment.
    Refer to the protocol for the complete list of criteria.
    1.Secondo l'opinione dello sperimentatore, il soggetto e/o il genitore o il tutore legale è in grado di comprendere e rispettare i requisiti del protocollo, compreso l'uso degli strumenti digitali, completare le valutazioni appropriate, mantenere un diario giornaliero accurato e completo delle crisi e assumere il farmaco dello studio per tutta la durata dello studio.
    2.Il soggetto o il genitore o il tutore legale del soggetto sono disposti e in grado di leggere, comprendere, e firmare e datare un modulo di consenso informato (ICF) scritto o elettronico, un modulo di assenso (se applicabile), e qualsiasi autorizzazione richiesta per la privacy prima dell'inizio di qualsiasi procedura dello studio.
    3.Il soggetto è maschio o femmina e di età compresa tra i 2 e i 21 anni, inclusi, al momento del consenso informato.
    4.Diagnosi clinica documentata di DS supportata da:
    -Insorgenza di crisi epilettiche di solito nel primo anno di vita.
    -Anamnesi di crisi epilettiche prolungate indotte dalla febbre, come determinato dallo sperimentatore:
    -Può includere crisi epilettiche emicloniche prolungate (circa 15 minuti o più).
    -Molteplici tipi di crisi epilettiche, che possono includere:
    -Tonico-cloniche generalizzate.
    -Tonico-cloniche da focali a bilaterali.
    -Cloniche.
    -Crisi miocloniche.
    -Anamnesi di ritardo nello sviluppo/disabilità intellettuale che si presenta dopo l'inizio delle crisi e che di solito si presenta dopo i 12 mesi di età.
    -Mutazione genetica documentata coerente con la DS non è richiesta, ma i risultati dei test genetici saranno raccolti se disponibili. Se il test genetico non è stato eseguito in precedenza o se il risultato di SCN1A è negativo (senza nessun altro gene positivo riportato che sia coerente clinicamente con la DS), il test per SCN1A sarà offerto al momento dello screening.
    5.Presenta =4 crisi convulsive in ciascun periodo di 1 mese nei 3 mesi precedenti lo screening in base ai dati anamnestici e presenta =4 crisi convulsive in 28 giorni durante il periodo basale prospettico da 4 a 6 settimane.
    6.Pesa =10 kg alla visita di screening (visita 1).
    7.Mancato controllo delle crisi epilettiche nonostante prove appropriate di almeno 2 ASM in base alle informazioni storiche ed è attualmente in terapia antiepilettica (ad esempio ASM, stimolazione del nervo vago (VNS), dieta chetogenica/modificata Atkins) o altre opzioni di trattamento considerate come SOC.
    8.Attualmente sta assumendo da 0 a 4 ASM a dosi stabili per almeno 4 settimane prima della visita di screening (Visita 1); le benzodiazepine usate cronicamente (quotidianamente) per trattare le crisi epilettiche sono considerate ASM. Il regime di dosaggio di ASM deve rimanere costante per tutto lo studio.
    9.Se si utilizza VNS, il soggetto deve avere un VNS posizionato almeno 3 mesi prima della visita di screening con impostazioni stabili per > 1 mese; i parametri VNS devono rimanere costanti per tutto lo studio (VNS non sarà conteggiato come un ASM).
    10.Se il soggetto segue una dieta chetogenica (o qualsiasi altra dieta utilizzata per il trattamento dell'epilessia, come la dieta Atkins modificata), deve aver iniziato la dieta almeno 3 mesi prima della visita di screening (Visita 1), e la dieta del soggetto deve essere stabile per 1 mese prima della visita di screening (Visita 1); il soggetto deve continuare questa dieta per tutta la durata dello studio (dieta chetogenica, o qualsiasi altra dieta per il trattamento dell'epilessia non sarà conteggiata come ASM).
    11.L'uso del felbamato è consentito a condizione che il soggetto non soddisfi i criteri di esclusione del test di funzionalità epatica (LFT), che la dose sia stata stabile per almeno 6 mesi prima dello screening e che il soggetto abbia avuto una funzionalità epatica stabile (come determinato dai livelli sierici di AST e ALT e dagli esami ematologici di laboratorio durante il corso del trattamento.
    Fare riferimento al protocollo per l'elenco complete dei criteri.
    E.4Principal exclusion criteria
    1. Investigator site personnel directly affiliated with this study and/or their immediate family. Note: Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
    2. Takeda employees or immediate family members.
    3. Currently enrolled in a clinical study involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or
    medically compatible with this study.
    Note: Compatibility will be determined based on consultation with the medical monitor or the sponsor.
    4. Participated in a clinical study involving another study drug in the last 30 days (or 5 half-lives of the study drug, whichever is longer) before screening (Visit 1).
    5. Received soticlestat in a previous clinical study.
    6. Known hypersensitivity to any component of the soticlestat formulation.
    7. Admitted to a medical facility and intubated for treatment of status epilepticus 2 or more times in the 3 months immediately before screening (Visit 1). Status epilepticus is defined as continuous seizure activity lasting longer than 5 minutes or repeated seizures without
    return to baseline in between seizures.
    8. Unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, ophthalmologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, endocrine disease, malignancy including progressive
    tumors, or other abnormality that may impact the ability to participate in the study or that may potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the medical monitor may be warranted.
    9. Any history of alcohol, opioid, or other drug use disorder, as per the
    Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSMV), within the 2 years immediately before the screening visit (Visit 1).
    10. Considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the subject has attempted suicide within 12 months before the screening visit (Visit 1). Subjects who have positive answers on item numbers 4 or 5 on the C-SSRS before
    randomization (Visit 2) are excluded. This scale will only be administered to subjects aged =6 years.
    11. History of HIV infection (subject has tested positive for HIV-1 or HIV-2 antibodies), history of hepatitis B infection, or current active hepatitis C infection.
    Note: Subjects who have been vaccinated against hepatitis B (hepatitis B surface antibody-positive] and who test negative for other markers of prior hepatitis B infection (eg, negative for hepatitis B core antibody) are eligible. Also note that subjects who test positive for hepatitis C antibody are eligible if they have a negative hepatitis C viral load by quantitative polymerase chain reaction.
    Refer to the protocol for the complete list of criteria.
    1. Membro del personale del centro dello sperimentatore direttamente coinvolto in questo studio e/o suo parente stretto.
    Nota:
    Si definiscono parenti stretti un coniuge, genitore, figlio, o fratello/sorella, biologici o legalmente adottati.
    2. Dipendenti Takeda o parenti stretti.
    3. Attualmente arruolato in uno studio clinico che coinvolge un prodotto sperimentale o l'uso non approvato di un farmaco o di un dispositivo (diverso dal prodotto sperimentale utilizzato in questo studio), o contemporaneamente arruolato a qualsiasi altro tipo di ricerca medica giudicata non compatibile scientificamente o dal punti di vista medico con questo studio.
    Nota:
    La compatibilità sarà determinata in base alla consultazione con il monitor medico o lo sponsor.
    4. Ha partecipato a uno studio clinico che coinvolge un altro farmaco in studio negli ultimi 30 giorni (o 5 emivite del farmaco di studio, qualunque sia il più lungo) prima dello screening (Visita 1).
    5. Ha ricevuto soticlestat in un precedente studio clinico.
    6. Nota ipersensibilità a qualsiasi componente della formulazione soticlestat.
    7. Ricoverato in una struttura medica e intubato per il trattamento dello stato epilettico 2 o più volte nei 3 mesi immediatamente precedenti lo screening (Visita 1). Lo stato epilettico è definito come attività convulsiva continua che dura più di 5 minuti o crisi ripetute senza ritorno al basale tra le crisi.
    8. Malattia neurologica instabile e clinicamente significativa (diversa dalla malattia in studio), psichiatrica, cardiovascolare, oftalmologica, polmonare, epatica, renale, metabolica, gastrointestinale, urologica, immunologica, ematopoietica, endocrina, tumori maligni compresa la progressione o altre anomalie che possono avere un impatto sulla capacità di partecipare allo studio o che possono potenzialmente confondere i risultati dello studio.
    È responsabilità dello sperimentatore valutare il significato clinico; tuttavia, la consultazione con il monitor medico può essere giustificata.
    9. Qualsiasi storia di disturbo da uso di alcol, oppioidi o altre droghe, secondo il Manuale diagnostico e statistico dei disturbi mentali, quinta edizione (DSM-V), nei 2 anni immediatamente precedenti la visita di screening (visita 1).
    10. Considerato dallo sperimentatore a rischio imminente di suicidio o lesioni a se stessi, agli altri o alla proprietà, o il soggetto ha tentato il suicidio entro 12 mesi prima della visita di screening (Visita 1).
    I soggetti che hanno risposte positive agli item numero 4 o 5 della C-SSRS prima della randomizzazione (visita 2) sono esclusi. Questa scala sarà somministrata solo a soggetti di età =6 anni.
    11. Storia di infezione da HIV (il soggetto è risultato positivo agli anticorpi HIV-1 o HIV-2), storia di infezione da epatite B o infezione da epatite C attualmente attiva.
    Nota:
    I soggetti che sono stati vaccinati contro epatite B (positivo all'anticorpo di superficie dell'epatite B) e che risultano negativi ad altri marcatori di una precedente infezione da epatite B (per esempio, negativi all'anticorpo di base dell'epatite B) sono eleggibili.
    Si noti inoltre che i soggetti che risultano positivi all'anticorpo dell'epatite C sono eleggibili se hanno una carica virale dell'epatite C negativa mediante reazione quantitativa a catena della polimerasi.
    Fare riferimento al protocollo per la lista completa dei criteri.
    E.5 End points
    E.5.1Primary end point(s)
    - Percent change from baseline in convulsive seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the full treatment period.

    - Percent change from baseline in convulsive seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the maintenance period.
    - Variazione percentuale dal basale nella frequenza delle crisi epilettiche per 28 giorni nei soggetti che ricevono soticlestat rispetto al placebo durante l'intero periodo di trattamento.
    - Variazione percentuale dal basale nella frequenza delle crisi epilettiche per 28 giorni nei soggetti che ricevono soticlestat rispetto al placebo durante il periodo di mantenimento.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary end points will be assessed throughout the study.
    Gli endpoint primari saranno valutati durante lo studio.
    E.5.2Secondary end point(s)
    - Proportion of responders defined as those with =50% reduction from baseline in convulsive seizures during the maintenance period and the full treatment period.
    - Percent change from baseline in frequency of all seizures per 28 days during the maintenance period and the full treatment period.
    - Percent change from baseline in convulsive seizure frequency per 28 days during the maintenance period.
    - Responder analysis of the proportion of subjects with =0%, >0% to =25%, >25% to =50%, >50% to =75%, and >75% to =100% reduction in convulsive seizures in a cumulative response curve.
    - Change from baseline in proportion of convulsive seizure-free days.
    - Longest convulsive seizure-free interval.
    - Number of days when rescue ASM is used.
    - CGI-I (clinician).
    - Care GI-I (caregiver).
    - CGI-I Seizure Intensity and Duration.
    - CGI-I Nonseizure Symptoms.
    - Change in QI-Disability score.
    Percentuale di responder definiti come quelli con =50% di riduzione dal basale nelle crisi epilettiche durante il periodo di mantenimento e il periodo di trattamento completo.
    Variazione percentuale dal basale nella frequenza di tutte le crisi per 28 giorni durante il periodo di mantenimento e il periodo di trattamento completo.
    Variazione percentuale dal basale nella frequenza delle crisi epilettiche per 28 giorni durante il periodo di mantenimento.
    Analisi della percentuale di responder con =0%, >0% a = 25%, >25% a =50%, >50% a =75%, e >75% a =100% di riduzione delle crisi epilettiche in una curva di risposta cumulativa.
    Variazione dal basale nella percentuale di giorni senza crisi epilettiche.
    L'intervallo di tempo più lungo libero da crisi epilettiche.
    Numero di giorni in cui vengono utilizzati ASM di salvataggio.
    - CGI-I (clinico).
    - Care GI-I (caregiver)
    - CGI-I Intensità e durata delle crisi
    - CGI-I Sintomi non epilettici
    - Cambiamento del punteggio QI-Disabilità.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary end points will be assessed throughout the study.
    Gli endpoint secondari saranno valutati durante lo studio.
    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 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 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 trial2
    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 EEA24
    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
    Belgium
    Canada
    China
    France
    Greece
    Hungary
    Italy
    Japan
    Latvia
    Netherlands
    Poland
    Russian Federation
    Serbia
    Spain
    Ukraine
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months22
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months22
    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) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 64
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 36
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 42
    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 state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 72
    F.4.2.2In the whole clinical trial 142
    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)
    Study drug will not be available upon completion of the subject’s participation in the study. The subject should be returned to the care of a physician and standard therapies initiated or resumed as required. However, following completion of the study, subjects will have the option to enroll in an OLE study, as per the OLE study’s inclusion/exclusion criteria.
    Il farmaco in studio non sarà disponibile al completamento della partecipazione del soggetto allo studio.
    Il soggetto dovrà tornare a ricevere le cure di un medico e iniziare o riprendere le terapie standard, come necessario.
    Tuttavia, dopo il completamento dello studio, i soggetti avranno la possibilità di arruolarsi ad uno studio OLE, secondo i criteri di inclusione/esclusione dello studio OLE.
    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 Decision2021-10-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-10-12
    P. End of Trial
    P.End of Trial StatusOngoing
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