E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Huntington´s disease |
Enfermedad de Huntigton |
|
E.1.1.1 | Medical condition in easily understood language |
Huntington´s disease |
Enfermedad de Huntigton |
|
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070668 |
E.1.2 | Term | Huntington's disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety and tolerability of combined oral thiamine with biotin therapy in patients with HD. |
Seguridad y tolerabilidad de la terapia combinada oral de tiamina con biotina en pacientes con EH. |
|
E.2.2 | Secondary objectives of the trial |
Demonstrate an increase in the level of thiamine monophosphate (TMP) in CSF of combined oral thiamine and biotin therapy in patients with HD |
Demostrar aumento del nivel de tiamina monofosfato (TMP) en LCR de la terapia combinada oral de tiamina y biotina en pacientes con EH |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
. Patients with Huntington's disease manifest with motor symptoms (chorea, dystonia or bradykinesia) and / or neuropsychiatric; and genetic confirmation of a number of repetitions of the CAG triplet in the HTT gene. . Patient older than or equal to 39 years . Women of childbearing age must obtain a negative result in the pregnancy test at the selection visit and accept the use of appropriate contraceptive methods throughout the course of the clinical trial and men who have a partner in childbearing age, accept the use of methods contraceptives |
. Pacientes con enfermedad de Huntington manifiesta con síntomas motores (corea, distonía o bradicinesia) y/o neuropsiquiátricos; y confirmación genética de un número de repeticiones del triplete CAG en el gen HTT. . Paciente mayor o igual a 39 años . Las mujeres en edad fértil deben obtener un resultado negativo en la prueba de embarazo en la visita de selección y aceptar el empleo de métodos anticonceptivos adecuados durante todo el transcurso del ensayo clínico y los varones que tengan pareja en edad fértil, aceptar el empleo de métodos anticonceptivos. |
|
E.4 | Principal exclusion criteria |
. Dependent patients for ABVD or with a degree of severe cognitive impairment that prevents participation / follow-up in the study (UHDRS TFC <7). . Patients with active psychosis at the time of clinical evaluation. . Pregnant or breastfeeding patients. . Advanced renal failure. |
. Pacientes dependientes para las ABVD o con un grado de deterioro cognitivo severo que impida la participación/seguimiento en el estudio (UHDRS TFC < 7). . Pacientes con psicosis activa en el momento de evaluación clínica. . Pacientes embarazadas o en periodo de lactancia. . Insuficiencia renal grado avanzado. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
. Evaluate the safety and tolerability of combined oral thiamine with biotin therapy in patients with mild to moderate stages of HH through physical examinations and biochemical tests in blood and urine, in addition to the collection of adverse events. |
. Evaluar la seguridad y tolerabilidad de la terapia combinada oral de tiamina con biotina en pacientes con EH en estadios leve a moderado mediante exámenes físicos y pruebas bioquímicas en sangre y en orina, además de la recogida de acontecimientos adversos. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
. Blood count, biochemistry and coagulation: Week 0,2,4,6,8,12,24, 36,48 and 52. . Physical exams (Blood pressure, heart rate, weight, height): Week 0,2,4,6,8,12,24, 36,48 and 52 . Evaluation of the patient's quality of life and overall (SF36, CGI-S and CGI-C scale): Week 0, 24 and 48 . Evaluation of disease and motor function: screening and Baseline visit and week 8, 24,36 and 48 |
. Hemograma, bioquímica y coagulación: Semana 0,2,4,6,8,12,24, 36,48 y 52 . Examenes físicos (Tensión arterial, frecuencia cardíaca, peso, talla): Semana 0,2,4,6,8,12,24, 36,48 y 52 . Evaluación de calidad de vida y global del paciente (Escala SF36, CGI-S y CGI-C): Semana 0, 24 y 48 . Evaluación de la enfermedad y función motora: visita de screening y Baseline y semana 8, 24,36 y 48 |
|
E.5.2 | Secondary end point(s) |
. To evaluate the biological effect of the treatment on the central nervous system using as a main biomarker the increase in the level of thiamine monophosphate (TMP) in CSF of these patients with HD during a one-year follow-up period, by lumbar puncture for the determination of NfL and thiamine (free, TMP, TPP) in CSF and skull MRI |
. Evaluar el efecto biológico del tratamiento en el sistema nervioso central utilizando como biomarcador principal el aumento del nivel de tiamina monofosfato (TMP) en LCR de estos pacientes con EH durante un período de seguimiento de un año, mediante analíticas, punción lumbar para la determinación de NfL y tiamina (libre, TMP, TPP) en LCR y en RM de cráneo |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
. MRI of the skull and lumbar puncture: week 0 (Baseline visit) and week 48 . Determination of thiamine (free, TMP, TPP) and plasma neurofilament light chain protein (NfL): Week 0 (visit Baseline), week 24 (visit 6), week 48 (visit 8) and week 52 (visit 9) |
. RM de cráneo y punción lumbar: semana 0 (visita de Baseline) y semana 48 . Determinación de tiamina (libre, TMP, TPP) y proteína de cadena ligera de neurofilamento (NfL) en plasma: Semana 0 (visita Baseline), semana 24 (visita 6), semana 48 (visita 8) y semana 52 (visita 9) |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | No |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial will be the last visit of the last subject |
El final del ensayo será la última visita del último sujeto. |
|
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 | |
E.8.9.1 | In the Member State concerned days | |