E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glucose Transporter Type 1 deficiency syndrome |
síndrome por deficiencia del transportador de glucosa de tipo 1 |
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E.1.1.1 | Medical condition in easily understood language |
Glucose transporter type 1 (Glut1) deficiency syndrome is a rare genetic metabolic disorder characterized by deficiency of a protein that is required for glucose to cross the blood-brain barrier |
El síndrome por deficiencia del transportador de glucosa de tipo 1 (Glut1) es una enfermedad metabólica rara caracterizada por la falta de una proteina necesaria para que la glucosa llegue al cerebro |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10039911 |
E.1.2 | Term | Seizures (incl subtypes) |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objectives: - Evaluate the efficacy of UX007 compared to placebo (between Weeks 2 and 8 of treatment), as measured by the reduction from the Baseline Period frequency of generalized or partial onset seizures - Evaluate the efficacy of UX007 compared to placebo in reducing the total frequency of absence seizures - Evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG) |
-Evaluar la eficacia de UX007 en comparación con un placebo (entre las Semanas 2 y 8 del tratamiento), medida por la reducción desde la frecuencia de crisis convulsivas generalizadas o de crisis convulsivas de inicio parcial durante el Período de Referencia -Evaluar la eficacia de UX007 en comparación con un placebo en la reducción de la frecuencia total de crisis de ausencia -Evaluar la seguridad de UX007 por medio de tasas de eventos adversos (AE, por sus siglas en inglés), valores de laboratorio y electrocardiogramas (ECG) |
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E.2.2 | Secondary objectives of the trial |
* Evaluate the efficacy of UX007 compared to placebo, as measured by: - Seizure response rate, defined as the % of subjects with at least 50% reduction from baseline period in generalized or partial-onset seizures, including absence seizures - Frequency of generalized or partial-onset seizures, including absence seizures - Change from randomization to Wk 8 in cognitive function using the Cambridge Neuropsychological Test Automated Battery - Change from randomization to Wk 8 in distance walked as measured by 6MWT - Time to onset of paroxysmal exertional dyskinesia as measured during 6MWT from randomization to Wk 8 - Change from randomization to Wk 8 in gross motor function using the Gross Motor Function Measure-88 * Evaluate long term efficacy as measured by changes from baseline in frequency of generalized or partial-onset seizures through Wk 52 * Evaluate the optimal dose to control seizures and impact on other clinical manifestations during the Dose Exploration Period |
* Evaluar la eficacia de UX007 en comparación con placebo, medido por: - Tasa de respuesta a crisis convulsivas, definidas como el porcentaje de sujetos con una reducción de al menos el 50% a partir del Período de Referencia en crisis convulsivas - Frecuencia de crisis convulsivas - Cambio desde la aleatorización hasta la Semana 8 en función cognitiva, - Cambio desde la aleatorización hasta la Semana 8 en distancia caminada - Tiempo hasta aparición de discinecia paroxística inducida por ejercicio medido durante 6MWT desde la aleatorización hasta la Semana 8 - Cambio desde la aleatorización hasta la Semana 8 en la motricidad gruesa *Evaluar la eficacia a largo plazo medida por los cambios desde el punto de referencia en la frecuencia de las crisis convulsivas * Evaluar la dosis óptima para controlar las crisis convulsivas y tener un impacto sobre otras manifestaciones clínicas durante el Período de Exploración de Dosis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Diagnosis of Glut1 DS confirmed by SLC2A1 mutation 2) Males and females, aged 1-35 years (inclusive) at the time of informed consent 3) Average of at least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, absence, or secondarily generalized] seizures) in 4 weeks over the last 24 weeks, by subject or caregiver report 4) At least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, or secondarily generalized] seizures) in 4 weeks during the Baseline Period, with no 3-week seizure-free period during the Baseline Period OR absence seizures documented on Screening EEG 5) Continuing to have seizures despite a prior or current use of at least 1 AED 6) Allowed to be on up to 3 concomitant AEDs that must have been stable in dose at least 2 weeks prior to the beginning of screening and anticipated to remain stable in dose through the end of the 8-week, placebo-controlled Treatment Period 7) Not on, or not fully compliant with a prescribed diet plan (e.g. ketogenic diet) comprised of at least 60% total daily caloric intake from fat during previous 14 days (confirmed by 3-day diet diary at Screening), or at any time during the course of the trial 8) Plasma level of beta-hydroxybutyrate (BHB) ? 1 mmol/L (non-fasting) at Screening 9) Provide written or verbal assent (if possible) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures 10) Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, comply with accurate completion of the seizures diary, and likely to complete the 8 week, placebo-controlled, Treatment Period 11) Females of childbearing potential must have a negative pregnancy test at Screening, be willing to use an acceptable method of contraception, and have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not reached menarche, had total hysterectomy, have been in menopause for at least two years, or have had tubal ligation at least one year prior to Screening |
1) Diagnóstico de Glut1 DS confirmado por una mutación en el SLC2A1 2) Hombres y mujeres de entre 1 y 35 años (inclusive) al momento de firmar el consentimiento informado 3) Un promedio de 2 crisis convulsivas observables (generalizadas o de inicio parcial) [crisis convulsivas parciales simples motoras, parciales complejas, de ausencia o generalizadas secundarias] en 4 semanas durante las últimas 24 semanas, determinadas por informe del sujeto o cuidador 4) Por lo menos 2 crisis convulsivas observables (generalizadas o de inicio parcial) [crisis convulsivas parciales simples motoras, parciales complejas o generalizadas secundarias] en 4 semanas durante el Período de Referencia, sin un período de 3 semanas sin convulsiones durante el Período de Referencia NI crisis de ausencia documentadas en el EEG 5) Seguir teniendo crisis convulsivas a pesar del uso actual o pasado de por lo menos 1 AED 6) Tiene permitido tomar hasta 3 AED concomitantes, que deben haber tenido una dosis estable por lo menos 2 semanas antes del comienzo de la selección y que se espera sigan teniendo una dosis estable hasta el final del Período de Tratamiento controlado con un placebo de 8 semanas 7) No debe haber estado realizando, o haber cumplido totalmente, un plan de dieta recetado (por ejemplo, KD) compuesto por al menos un 60% de la ingesta calórica diaria de grasas durante los 14 días interiores (confirmado por un diario de dieta de 3 días durante la Selección), ni en ningún momento durante el curso del ensayo 8) Nivel plasmático de beta hidroxibutirato (BHB) ? 1 mmol/L (sin estar en ayunas) en la Selección 9) Provisión de consentimiento escrito o verbal (de ser posible) y consentimiento informado escrito por parte de un representante legalmente autorizado después de que se haya explicado la naturaleza del estudio, y antes de cualquier procedimiento relacionado con la investigación 10) Debe, en la opinión del investigador, estar dispuesto a completar todos los aspectos del estudio, completar de manera precisa el diario de crisis convulsivas, y tener probabilidad de completar el Período de Tratamiento de 8 semanas controlado con un placebo, y pode hacerlo 11) Las mujeres en edad reproductiva deben realizar una prueba de embarazo y obtener un resultado negativo durante la Selección, estar dispuestas a utilizar un método anticonceptivo aceptable, y realizarse pruebas de embarazo adicionales durante el estudio. Las mujeres que no se considera tienen potencial reproductivo incluyen aquellas que no han tenido la menarca, que se realizaron una histerectomía total, que han estado en la menopausia durante por lo menos dos años, o que se hicieron una ligadura de trompas por lo menos un año antes de la Selección. |
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E.4 | Principal exclusion criteria |
1) Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2X the upper limit of normal at Screening 2) Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the investigator, places the subject at increased risk for adverse effects 3) Prior use of triheptanoin within 30 days prior to Screening 4) History of, or current suicidal ideation, behavior and/or attempts 5) Pregnant and/or breastfeeding an infant at Screening 6) Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives 7) Use of any investigational product (drug or supplement, including medium chain triglyceride [MCT] oil) within 30 days prior to Screening, or at any time during the study 8) Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment 9) Has a concurrent disease or condition, or laboratory abnormality that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns (e.g., diabetes mellitus, other concurrent neurological or psychiatric disorders) |
1) Concentraciones séricas de alanina aminotransferasa (ALT) o aspartato aminotransferasa (AST) que superan el doble del límite superior del nivel normal en la Selección 2) Cualquier hipersensibilidad conocida a la triheptanoína o al aceite de alazor que, a juicio del investigador, ponga al sujeto en mayor riesgo de sufrir efectos adversos 3) Uso anterior de triheptanoína en los 30 días anteriores a la Selección 4) Antecedentes de pensamientos, comportamientos o intentos suicidas, o pensamientos, comportamientos o intentos suicidas actuales 5) Embarazada y/o amamantando a un bebé al momento de la Selección 6) Participantes que no estén dispuestos a discontinuar o no puedan discontinuar el uso de un medicamento prohibido u otra sustancia que podría confundir los objetivos del estudio 7) El uso de cualquier producto en investigación (fármaco o suplemento, incluyendo aceites triglicéridos de cadena media [MCT, por sus siglas en inglés]) en los 30 días anteriores a la Selección, o en cualquier momento durante el estudio 8) Tiene una enfermedad tan grave y aguda, en la opinión del investigador, que necesita intervención quirúrgica inmediata u otro tratamiento 9) Tiene una enfermedad concurrente, o anormalidad de laboratorio que, en la opinión del investigador, pone al sujeto en alto riesgo de muy mal cumplimiento con el tratamiento o de no completar el estudio, o que interferiría con la participación en el estudio o introduce preocupaciones de seguridad adicionales (por ejemplo, diabetes melitus, otros trastornos neurológicos o psiquiátricos concurrentes) |
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E.5 End points |
E.5.1 | Primary end point(s) |
? Seizure frequency: The number of observable seizures recorded via patient-reported diary between Weeks 2 and 8 of treatment. Observable seizures include: Generalized Tonic-Clonic, Generalized Tonic, Generalized Clonic, Generalized Atonic, Partial/Focal with Secondary Generalization, Myoclonic, Myoclonic Atonic, Myoclonic Tonic, Complex Partial/Focal, and Simple Partial/Focal Motor. The frequency of each seizure type will be recorded.
? Seizure frequency: The number of absence seizures recorded via EEG in those subjects who enrolled secondary solely to a history of absence seizures confirmed on Screening EEG. |
véase en el resumen del protocolo en castellano |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
? Observable seizures: Between Weeks 2 and 8 ? Absence seizures: Weeks 0, 8, 26, and 31 |
véase en el resumen del protocolo en castellano |
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E.5.2 | Secondary end point(s) |
? Seizure response rate, defined as the percentage of subjects with at least 50% reduction from Baseline Period in generalized or partial-onset seizures or absence seizures between Weeks 2 and 8 of treatment via the patient reported diary ? Seizure response rate, defined as the percentage of subjects with at least 50% reduction in absence seizures between Baseline EEG and Week 8 EEG. ? Frequency of generalized or partial-onset seizures via patient reported diary ? Frequency of absence seizure (recorded via EEG) ? Cambridge Neuropsychological Test Automated Battery: Neuropsychological function measured using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time ? Six Minute Walk Test: Walking ability measured by the total distance walked (meters) in a 6-minute period. The percent of predicted normal distance walked will be determined. ? Paroxysmal Exertional Dyskinesia: Time to onset of PED as observed during the 6MWT ? Gross Motor Function Measure-88: Gross motor function evaluated using a standardized observational measure of abilities in the following 5 domains: lying/rolling, sitting, crawling/kneeling, standing, and walking/running/jumping |
véase en el resumen del protocolo en castellano |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
? Observable seizures: Between Weeks 2 and 8 ? Absence seizures: Weeks 0, 8, 26, and 31 ? Cognitive and Motor Evaluations: Timepoints upto 52 weeks |
véase en el resumen del protocolo en castellano |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
periodo de extensión de etiqueta abierta tras las 8 semanas de doble ciego |
open-label Extension Period after the initial 8-week double-blind |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Hungary |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial 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
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Last patient last visit |
Última visita del último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |