E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ADRENOMYELONEUROPATHY IN MALE PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY |
ADRENOMIELONEUROPATÍA EN VARONES CON ADRENOLEUCODISTROFIA LIGADA AL CROMOSOMA X |
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E.1.1.1 | Medical condition in easily understood language |
ADRENOMYELONEUROPATHY |
ADRENOMIELONEUROPATÍA |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 |
Main Study: Efficacy of MIN-102 on the progression of adrenomyeloneuropathy (AMN) in male patients as determined by the change from baseline in Six-Minute Walk Test (6MWT) compared with placebo after 96 weeks of treatment.
Extension Study: To assess the safety and tolerability of MIN-102 upon long-term treatment. |
Estudio principal: Eficacia de MIN-102 sobre la progresión de la adrenomieloneuropatía (AMN) en varones de acuerdo con el cambio con respecto a los valores iniciales en la prueba de marcha de 6 minutos (6MWT) en comparación con placebo tras 96 semanas de tratamiento. Estudio de extension: Evaluar la seguridad y tolerabilidad de MIN-102 con el tratamiento a largo plazo |
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E.2.2 | Secondary objectives of the trial |
Main Study: Efficacy objectives: To evaluate the effects of MIN-102 after 96 weeks of treatment on: • Change from baseline in body sway amplitude • Comprehensive clinical rating scales (SSPROM and EDSS) • Clinician and patient global impression of symptom severity and change • Muscle strength • Quality of life • Incidence of cerebral inflammatory lesions. Safety objectives: To evaluate the safety and tolerability of MIN-102 compared with placebo Exploratory objectives- To evaluate the effects of MIN-102 on various biochemical markers in plasma and cerebrospinal fluid (CSF), and spinal cord imaging parameters.
Extension Study: To evaluate the long-term effects of MIN-102 on: • Change from baseline in 6MWT and body sway • Comprehensive clinical rating scales (SSPROM and EDSS) • Quality of life • Incidence of cerebral inflammatory lesions. Exploratory objectives- To assess the long-term effects of MIN-102 on various biochemical markers in plasma. |
Estudio principal:Objetivos eficacia: Evaluar efectos de MIN-102 tras 96 semanas de tratam. sobre: cambio respecto a valores iniciales en amplitud de balanceo del cuerpo;escalas puntuación clínica exhaustiva (SSPROM y EDSS);impresión global médico y paciente sobre intensidad y cambio de síntomas;fuerza muscular; calidad de vida;incidencia lesiones cerebrales inflamatorias.Objetivos seguridad.Evaluar seguridad y tolerabilidad de MIN-102 en comparac con placebo.Objetivos exploratorios.Evaluar efectos de MIN-102 sobre varios marcadores bioquím. en plasma y líquido cefalorraquídeo(LCR), y parámetros de obtención imágenes de méd. espinal.Estudio extension:Evaluar efectos a largo plazo de MIN-102 sobre:cambio con resp. a valores iniciales en prueba 6MWT y balanceo cuerpo;escalas puntuación clínica exhaustiva (SSPROM y EDSS);calidad vida;incidencia lesiones cerebrales inflamatorias.Objetivos exploratorios:Evaluar efectos a largo plazo de MIN-102 sobre varios marcadores bioquímicos en plasma. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional CSF Sampling Sub-Study (integral part of Protocol Version 1.0 dated 26 Apr 2017) Objective: To evaluate the effects of MIN-102 on various biochemical markers in plasma and cerebrospinal fluid (CSF).
Optional Spinal Cord MRI scan Sub-study (integral part of Protocol Version 1.0 dated 26 Apr 2017) Objective: To evaluate the effects of MIN-102 on spinal cord imaging parameters. |
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E.3 | Principal inclusion criteria |
Main Study: 1. Male patients aged ≥18 to ≤65 years. 2. Diagnosis of ALD based on elevated very long-chain fatty acids (VLCFA) and genetic testing 3. Clinical evidence of spinal cord involvement, with an EDSS score between 2 and 6 4. Ability to walk for 6 minutes, without or with rest, with usual walking aids (cane or walker) 5. Ability to stand on a force plate with closed eyes and with feet apart for a minimum of 20 seconds 6. Either a normal brain MRI or a type-3 pattern MRI abnormality in which the abnormality is considered to represent the centripetal extension of the distal axonopathy 7. Normal adrenal function or appropriate steroid replacement if adrenal insufficiency is present.
Extension Study: 1. Consent to participate in the extension study part 2. Completion of the entire 96-weeks double-blind period of the study (Part 1) and consent to participate in the extension study part 3. Normal adrenal function or appropriate steroid replacement |
Estudio principal: 1.Varones de ≥ 18 a ≤ 65 años de edad. 2.Tener un diagnóstico de ALD basado en una elevación de los ácidos grasos de cadena muy larga (AGCML) y pruebas genéticas. 3.Tener pruebas clínicas de afectación de la médula espinal, con una puntuación EDSS entre 2 y 6. 4.Capacidad para caminar durante 6 minutos, sin o con descanso, con los dispositivos de ayuda para caminar habituales (bastón o andador). 5.Capacidad para permanecer de pie sobre una plataforma de fuerza con los ojos cerrados y con los pies separados durante un mínimo de 20 segundos 6.Tener una RM del cerebro normal o bien una anomalía en la RM de patrón tipo 3 en la que se considere que la anomalía representa la extensión centrípeta de la axonopatía distal 7.Tener una función suprarrenal normal o reemplazo de esteroides apropiado si existe una insuficiencia suprarrenal. Estudio de esxtensión: 1.Aportar el consentimiento informado por escrito para participar en la parte del estudio de extension 2.Finalizar el periodo entero doble ciego de 96 semanas del estudio (parte 1). 3.función suprarrenal normal o reemplazo de esteroides apropiado |
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E.4 | Principal exclusion criteria |
Main Study & Extension Study: 1. Any other chronic neurological disease with signs of spastic paraplegia 2. Known type 1 or type 2 diabetes. 3. Known intolerance to pioglitazone or any other thiazolidinedione. 4. Previous or current use of honokiol, pioglitazone or other thiazolidinediones, biotin (MD-1003), unstable dose of Lorenzo's oil 5. Current treatment with immunosuppressant medication, except for corticosteroids. 6. Previous or current history of cancer, bone marrow transplantation, Congestive heart failure, significant liver and renal disorders, anemia, pulmonary or cardiac diseases, Cognitive or behavioral abnormalities, alcohol/drug abuse etc. |
Estudio principal y de extension: 1.Cualquier otra enfermedad neurológica crónica con signos de paraplejía espástica. 2.Diabetes conocida de tipo 1 o tipo 2. 3. Intolerancia conocida a la pioglitazona o a cualquier otra tiazolidinediona 4.Pacientes que estén tomando o hayan tomado honokiol, pioglitazona u otras tiazolidinedionas, biotina (MD-1003), dosis no estable de aceite de Lorenzo. 5.Tratamiento actual con inmunodepresores, excepto los corticoesteroides 6.Antecedentes previos o actuales de cancer, trasplante de médula ósea, insuficiencia cardíaca congestiva, enfermedad hepatica o renal significativa, anemia, nefermedad pulmonary o cardiac, Anomalías cognitivas o conductuales, alcoholismo y/o drogadicción, etc |
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E.5 End points |
E.5.1 | Primary end point(s) |
Main Study: 1. Efficacy: Change from baseline to week 96 in the total walking distance in the 6MWT
Extension Study: 1. Long-term safety and tolerability assessed in terms of AE, SAE, SUSARs, Vitals signs, ECG, Clinical Laboratory tests |
Estudio principal: 1.Eficacia: cambio con respecto a los valores iniciales hasta la semana 96 en la distancia total recorrida en la prueba 6MWT
Estudio de extension: 1. Seguridad y tolerabilidad a largo plazo de MIN-102, que se evaluará en términos de AA, AAG y SRAGI, constantes vitales, análisis clínicos de laboratorio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During treatment period |
Durante el periodo de tratamiento |
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E.5.2 | Secondary end point(s) |
Main Study: 1. Changes from baseline to week 96 in the following: • Body sway amplitude • Comprehensive clinical rating scales (SSPROM, EDSS) • Clinician and patient global impression Scales (CGI-S, CGI-I, PGI-I) • Dynamometry • Quality of Life Assessments (EQ-5D-5L, MSWS-12, Qualiveen-SF and IIEF) • Cerebral MRI (incidence of inflammatory lesions) 2. Safety : Assessed in terms of AE, SAE, SUSARs, Vitals signs, ECG, Clinical Laboratory tests
Extension Study: Changes from the baseline to the last scheduled on-study assessment for the following variables: • 6MWT • Body sway amplitude • Comprehensive clinical rating scales (SSPROM, EDSS) • Quality of Life Assessments (EQ-5D-5L, MSWS-12, Qualiveen-SF and IIEF) • Cerebral MRI (incidence of inflammatory lesions) |
Estudio principal: 1.Cambios con respecto a los valores iniciales hasta la semana 96 en: -La amplitud de balanceo del cuerpo -Las escalas de puntuación clínica exhaustiva (SSPROM y EDSS). - Escalas para la impresión global del médico y el paciente (CGI-S, CGI-I, PGI-I) -Cuestionarios de calidad de vida (EQ-5D-5L, MSWS-12, Qualiveen-SF y IIEF) -RM del cerebro (incidencia de lesiones cerebrales inflamatorias). 2. Seguridad: Seguridad Se evaluará la seguridad en términos de de AA, AAG y SRAGI, constantes vitales, análisis clínicos de laboratorio. Estudio de extension: Cambios con respecto a los valores iniciales de la parte 2 (V6) hasta la última evaluación durante el estudio programada para las siguientes variables: -6MWT -La amplitud de balanceo del cuerpo - Escalas de puntuación clínica exhaustiva (SSPROM y EDSS); - Evaluaciones de la calidad de vida (EQ-5D-5L, MSWS-12, Qualiveen-SF y IIEF). - RM del cerebro (incidencia de lesiones cerebrales inflamatorias). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During treatment period |
Durante el periodo de tratamiento |
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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 | Yes |
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) | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
El estudio principal es aleatorizado, controlado, doble ciego y el estudio de extensión es abierto |
Main Study is Randomized, Controlled, Double-Blind and Extension Study is Open-Label |
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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 | 7 |
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 |
Germany |
Hungary |
Italy |
Netherlands |
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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Main Study: LVLS (expected duration of trial is 3 years after which Clinical Study Report (CSR) will be written)
Extension Study: LVLS (expected duration of trial cannot be estimated since it will be for unlimited time in principle) |
Estudio principal: Última Visita del úlltimo Sujeto (la duración esperada del ensayo es de 3 años tras lo cual se escribirá el Informe Final del Ensayo
Estudio de extension: Última Visita del úlltimo Sujeto (la duración del ensayo no puede estimarse ya que en principio será por un tiempo ilimitado) |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |