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    Summary
    EudraCT Number:2021-002481-40
    Sponsor's Protocol Code Number:TAK-935-3002
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-07-27
    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 number2021-002481-40
    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 Adult Subjects With Lennox-Gastaut Syndrome (LGS)
    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 adulti affetti da sindrome di Lennox-Gastaut (LGS)
    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 Adult Subjects With Lennox-Gastaut Syndrome
    Studio su soticlestat come terapia aggiuntiva in soggetti pediatrici e adulti affetti da sindrome di Lennox-Gastaut
    A.3.2Name or abbreviated title of the trial where available
    Skyway
    Skyway
    A.4.1Sponsor's protocol code numberTAK-935-3002
    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 number000000
    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
    Lennox-Gastaut Syndrome (LGS)
    Sindrome di Lennox-Gastaut (LGS)
    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 20.1
    E.1.2Level PT
    E.1.2Classification code 10048816
    E.1.2Term Lennox-Gastaut syndrome
    E.1.2System Organ Class 10029205 - Nervous system 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 assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on therapy to standard of care (SOC) as compared with placebo during the full treatment period (titration + maintenance).

    For EMA registration:
    - To assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on
    therapy to SOC compared with placebo during the maintenance period only.
    - Valutare l’efficacia e la sicurezza di soticlestat nel ridurre la frequenza delle crisi convulsive con crisi motoria maggiore (Major Motor Drop, [MMD]) come terapia aggiuntiva allo standard di cura (Standard Of Care, [SOC]) rispetto al placebo durante l’intero periodo di trattamento (titolazione + mantenimento).

    Per la registrazione presso l’Agenzia Europea per i medicinali (European Medicines Agency, [EMA]):
    - Valutare l’efficacia e la sicurezza di soticlestat nel ridurre la frequenza delle crisi convulsive con MMD come terapia aggiuntiva al SOC rispetto al placebo solo durante il 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 MMD 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 MMD seizure-free days.
    - Longest MMD seizure-free interval.
    - Number of days when rescue 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 caregiver.
    - Effect on Quality of Life Inventory-Disability (QI-Disability).
    Valutare quanto segue nei sub che assumono soticlestat rispetto al placebo per l’intero periodo di trattamento, salvo se diversamente indicato:
    - Percentuale di responder al trattamento, definiti come sub con riduzione =50% delle crisi convulsive con MMD dal basale per il periodo di mantenimento e l’intero periodo di trattamento
    - Effetto sulla frequenza totale di tutti i tipi di crisi convulsive per il periodo di mantenimento e l’intero periodo di trattamento
    - Variazione rispetto al basale nella percentuale di gg senza crisi convulsive con MMD
    - Intervallo senza crisi convulsive con MMD più lungo
    - Numero di gg in cui vengono usati farmaci ASM
    - Effetto sulla CGI-I da parte del medico e Care GI-I da parte del caregiver
    - Effetto sull’intensità e sulla durata delle crisi convulsive scala CGI-I
    - Effetto sui sintomi non associati a crisi convulsive scala CGI-I compilata dal medico con il contributo del caregiver
    - Effetto sul Questionario QI-Disability
    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 before the initiation of any study procedures.
    3. The subject is male or female and aged 2 to 35 years, inclusive, at the time of informed consent.
    4. Documented clinical diagnosis of LGS supported by:
    – Onset of seizures usually between the ages of 1 and 8 years.
    – Presence of multiple seizure types: including drop seizures (eg, tonic-atonic seizures) and other seizure types including atypical absence seizures, tonic-clonic, myoclonic, and partial seizures.
    – History of abnormal EEG (eg, slow spike and wave [<2.5 Hz], slow or disorganized EEG background, generalized paroxysmal fast activity).
    – Developmental delay or intellectual disability consistent with LGS.
    5. The participant has =8 MMD seizures each month in the 3 months prior to screening based on the historical information and has =8 MMD 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 anti-seizure therapy (eg, ASMs, vagus nerve stimulation (VNS), ketogenic/modified Atkins diet), or other treatment options considered as SOC.
    8. Currently taking 0 to 3 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; and 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); 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.
    12. Approved to participate by the sponsor and/or designee (ie, TESC) after review of medical history and seizure classification.
    For the complete list of criteria refer to the protocol.
    1. A giudizio dello sperimentatore, il soggetto e/o il genitore o tutore legale è/sono in grado di comprendere e attenersi ai requisiti dello studio, compreso l’uso di strumenti digitali, completare le valutazioni appropriate, mantenere un diario delle crisi convulsive giornaliero accurato e completo e assumere il farmaco dello studio per tutta la durata dello studio.
    2. Il soggetto o il suo genitore o tutore legale è disposto e in grado di leggere, comprendere e firmare e datare un modulo di consenso informato (Informed Consent Form, [ICF]) in formato elettronico o cartaceo, un modulo di assenso (se pertinente) e qualsiasi autorizzazione sulla privacy richiesta prima dell’avvio di qualsiasi procedura dello studio.
    3. Il soggetto è di sesso maschile o femminile e di età compresa tra 2 e 35 anni (inclusi) al momento del consenso informato.
    4. Diagnosi clinica documentata di LGS supportata da:
    - Insorgenza di crisi convulsive generalmente tra 1 e 8 anni di età.
    - Presenza di più tipi di crisi convulsive: comprese crisi convulsive con caduta (ad es., crisi convulsive tonico-atoniche) e altri tipi di crisi convulsive, tra cui crisi convulsive con assenze atipiche, crisi convulsive tonico-cloniche, miocloniche e parziali.
    - Anamnesi di elettroencefalogramma (EEG) anomalo (ad es., punta-onda lenta [<2,5 Hz], attività EEG di fondo lenta o disorganizzata, attività parossistica rapida generalizzata).
    - Ritardo dello sviluppo o invalidità intellettiva coerente con la LGS.
    5.Il partecipante presenta =8 crisi convulsive con MMD ogni mese nei 3 mesi precedenti lo screening in base ai dati anamnestici e =8 crisi convulsive con MMD in 28 giorni durante il periodo basale prospettico da 4 a 6 settimane.
    6. Peso =10 kg alla visita di screening (Visita 1).
    7. Mancato controllo delle crisi convulsive nonostante sperimentazioni appropriate di almeno 2 ASM in base alle informazioni storiche e terapia anticonvulsivante in corso (ad es., ASM, stimolazione del nervo vago [SNV], dieta chetogenica/Atkins modificata)
    o altre opzioni di trattamento considerate SOC.
    8. Attuale assunzione di 0-3 ASM a dosi stabili per almeno 4 settimane prima della visita di screening (Visita 1); le benzodiazepine utilizzate cronicamente (ogni giorno) per trattare le crisi convulsive sono considerate ASM. Il regime di dosaggio degli ASM deve rimanere costante per tutta la durata dello studio.
    9. Se si utilizza una SNV, il soggetto deve essersi sottoposto a SNV almeno 3 mesi prima della visita di screening con impostazioni stabili per >1 mese e i parametri SNV devono rimanere costanti per tutta la durata dello studio (la SNV non sarà conteggiata come ASM).
    10. In caso di dieta chetogenica (o qualsiasi altra dieta utilizzata per il trattamento dell’epilessia, come la dieta Atkins modificata), il soggetto 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); inoltre, il soggetto deve continuare questa dieta per tutta la durata dello studio (la dieta chetogenica o qualsiasi altra dieta per il trattamento dell’epilessia non sarà conteggiata come ASM).
    11. L’uso di felbamato è consentito a condizione che il soggetto non soddisfi i criteri di esclusione relativi ai test di funzionalità epatica (Liver Function Test, [LFT]), che la dose sia stabile da almeno 6 mesi prima dello screening e che il soggetto abbia presentato valori stabili nella funzionalità epatica (determinata in base ai livelli sierici di aspartato aminotransferasi [AST] e alanina aminotransferasi [ALT]) e negli esami ematologici di laboratorio durante il corso del trattamento.
    12. Autorizzazione a partecipare da parte dello sponsor e/o da un suo designato (ovvero, TESC) previa revisione dell’anamnesi medica e classificazione delle crisi convulsive.
    Per la lista completa dei criteri fare riferimento al protocollo.
    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 halflives 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 (DSM-V), 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/dosing (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 antibodypositive]
    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 exclusion criteria.
    1. Personale del centro dello sperimentatore direttamente affiliato a questo studio e/o ai rispettivi familiari stretti. Nota: per familiari stretti si intendono coniugi, genitori, figli o fratelli/sorelle, sia biologici sia legalmente adottati.
    2. Dipendenti Takeda o familiari stretti.
    3. Attuale arruolamento in uno studio clinico che coinvolga un prodotto sperimentale o l’uso non approvato di un farmaco o dispositivo (diverso dal prodotto sperimentale utilizzato in questo studio) o arruolamento concomitante in qualsiasi altro tipo di ricerca medica ritenuta non scientificamente o clinicamente compatibile con questo studio. Nota: la compatibilità sarà determinata in base a un consulto con il responsabile del monitoraggio medico o lo sponsor.
    4. Partecipazione a uno studio clinico che coinvolga un altro farmaco dello studio negli ultimi 30 giorni (o 5 emivite del farmaco dello studio, a seconda di quale periodo sia più lungo) prima dello screening (Visita 1).
    5. Assunzione di soticlestat in un precedente studio clinico.
    6. Ipersensibilità nota a qualsiasi componente della formulazione di soticlestat.
    7. Ricovero in una struttura medica e intubazione 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 convulsive ripetute senza ritorno al basale tra una crisi e l’altra.
    8. Malattia neurologica instabile, clinicamente significativa (diversa dalla malattia oggetto di studio), psichiatrica, cardiovascolare, oftalmologica, polmonare, epatica, renale, metabolica, gastrointestinale, urologica, immunologica, ematopoietica, endocrina, neoplasia maligna, inclusi i tumori progressivi, o altra anomalia che potrebbe influire sulla capacità di partecipare allo studio o che potrebbe potenzialmente confondere i risultati dello studio. È responsabilità dello sperimentatore valutare la significatività clinica; tuttavia, può essere giustificato un consulto con il responsabile del monitoraggio medico.
    9. Qualsiasi anamnesi di disturbo da uso di alcol, oppioidi o altri farmaci, come indicato nel Manuale diagnostico e statistico dei disturbi mentali, 5¿ edizione (Diagnostic and Statistical Manual of Mental Disorders, [DSM-V]), nei 2 anni immediatamente precedenti la visita di screening (Visita 1).
    10. Il soggetto è considerato dallo sperimentatore a rischio imminente di suicidio o lesione a se stesso, agli altri o alla proprietà, oppure ha tentato il suicidio entro 12 mesi prima della visita di screening (Visita 1). Sono esclusi i soggetti che hanno fornito risposte positive alla voce n. 4 o 5 sulla Scala della Columbia University per la valutazione della gravità del rischio di suicidio (Columbia Suicide Severity Rating Scale, [C-SSRS]) prima della randomizzazione/somministrazione (Visita 2). Questa scala sarà somministrata solo a soggetti di età =6 anni.
    11. Anamnesi di infezione da virus dell’immunodeficienza umana (Human Immunodeficiency Virus, [HIV]) (il soggetto è risultato positivo al test degli anticorpi anti-HIV-1 o anti-HIV-2), anamnesi di infezione da epatite B o attuale infezione attiva da epatite C.
    Nota: i soggetti che sono stati vaccinati contro l’epatite B (positivi agli anticorpi di superficie dell’epatite B)
    e che risultano negativi agli altri marcatori della precedente infezione da epatite B (ad es. negativi agli anticorpi core dell’epatite B) sono idonei. Si noti inoltre che i soggetti che risultano positivi al test degli anticorpi anti-epatite C sono idonei purché presentino una carica virale dell’epatite C negativa mediante reazione a catena della polimerasi quantitativa.
    Fare riferimento al protocollo per la lista completa dei criteri di esclusione
    E.5 End points
    E.5.1Primary end point(s)
    - Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the full treatment period.
    For EMA registration:
    - Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the maintenance period.
    - Variazione percentuale rispetto al basale nella frequenza delle crisi convulsive con MMD su 28 giorni nei soggetti che ricevono soticlestat rispetto al placebo durante l’intero periodo di trattamento.
    Per la registrazione presso l’EMA:
    - Variazione percentuale rispetto al basale nella frequenza delle crisi convulsive con MMD su 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 tutto lo studio.
    E.5.2Secondary end point(s)
    To assess the following in subjects receiving soticlestat as compared with placebo during the full treatment period, unless otherwise noted:
    - Proportion of responders defined as those with =50% reduction from baseline in MMD 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 MMD 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 from baseline in MMD seizures in a cumulative response curve.
    - Change from baseline in proportion of MMD seizure-free days.
    - Longest MMD 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.
    Valutare quanto segue nei soggetti che ricevono soticlestat rispetto al placebo durante l’intero periodo di trattamento, salvo se diversamente indicato:
    - Percentuale di responder definiti come soggetti con riduzione =50% rispetto al basale nelle crisi convulsive con MMD durante il periodo di mantenimento e l’intero periodo di trattamento.
    - Variazione percentuale rispetto al basale nella frequenza di tutte le crisi convulsive su 28 giorni durante il periodo di mantenimento e l’intero periodo di trattamento.
    - Variazione percentuale rispetto al basale nella frequenza delle crisi convulsive con MMD su 28 giorni durante il periodo di mantenimento.
    - Analisi dei responder della percentuale di soggetti con riduzione =0%, da >0% a =25%, da >25% a =50%, da >50% a =75% e da >75% a =100% rispetto al basale delle crisi convulsive con MMD in una curva di risposta cumulativa.
    - Variazione rispetto al basale nella percentuale di giorni senza crisi convulsive con MMD.
    - Intervallo senza crisi convulsive con MMD più lungo.
    - Numero di giorni in cui viene utilizzato l’ASM di soccorso.
    - CGI-I (medico).
    - Care GI-I (caregiver).
    - Intensità e durata delle crisi convulsive secondo la scala CGI-I.
    - Sintomi non associati a crisi convulsive secondo la scala CGI-I.
    - Variazione nel punteggio QI-Invalidità.
    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 tutto 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 EEA4
    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
    China
    Japan
    Russian Federation
    Serbia
    Ukraine
    United States
    Belgium
    France
    Hungary
    Italy
    Latvia
    Netherlands
    Poland
    Spain
    United Kingdom
    Greece
    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: 105
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 59
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 70
    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 114
    F.4.2.2In the whole clinical trial 234
    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 una volta completata la partecipazione del soggetto allo studio. Il soggetto deve essere restituito alle cure di un medico e alle terapie standard iniziate o riprese come richiesto. Tuttavia, dopo il completamento dello studio, i soggetti avranno la possibilità di arruolarsi in uno studio di estensione in aperto (Open-Label Extension, [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 StatusCompleted
    P.Date of the global end of the trial2023-11-23
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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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