E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune refractory epilepsy and Rasmussen Encephalitis |
Epilepsia refractaria de origen autoinmune y encefalitis de Rasmussen |
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E.1.1.1 | Medical condition in easily understood language |
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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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of intra-arterial administration of autologous mesenchymal stem cells in patients with immune-mediated refractory epilepsies. |
Evaluar la seguridad y tolerabilidad de la administración intra-arterial de células madre mesenquimales autólogas en pacientes con epilepsias refractarias inmunomediadas. |
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E.2.2 | Secondary objectives of the trial |
- To assess the clinical response to intra-arterial administration of autologous bone marrow mesenchymal cells by detecting any changes in the neurological assessments, neuropsychological evaluations, structural and functional neuroimaging tests, and neurophysiological tests. - Determine the effect of therapy on the patient's immune system and mRNA profile, both peripherally (peripheral blood) and locally in the primary sample obtained during surgery. - To study the molecular profile of the mesenchymal stem cells used in the trial and correlate them with the clinical outcome. |
- Evaluar la respuesta clínica de la administración vía intra-arterial de células mesenquimales autólogas de médula ósea mediante la detección de algún tipo de cambio en evaluaciones neurológicas, evaluaciones neuropsicológicas, pruebas de neuroimagen estructural y funcional, y pruebas neurofisiológicas. - Determinar el efecto de la terapia sobre el sistema inmunológico de los pacientes y el perfil de ARNm, en periféria (sangre periférica) y localmente en la muestra primaria obtenida durante la cirugía. - Estudiar el perfil molecular de las células madre mesenquimales utilizadas en el ensayo y correlacionarlas con el resultado clínico. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Acceptance of informed consent. 2. Paediatric population under 16 years of age. 3. Epilepsy of immune etiology refractory to first or second line treatment (antiepileptic drugs and conventional immunomodulatory therapy) in which motor and/or cognitive impairment is observed. A special group will be those undergoing epilepsy surgery in the context of Rasmussen's Encephalitis. 4. Possibility of performing CMR, electrophysiological tests, PET and neuropsychological evaluations. |
1. Aceptación del consentimiento informado. 2. Población pediátrica menor de 16 años. 3. Epilepsia de etiología inmune refractaria a primera o segunda línea de tratamiento (fármacos antiepilépticos y terapia inmunomoduladora convencional) en los que se objetiva un deterioro motor y/o cognitivo. Un grupo especial serán aquellos que se someterán a una cirugía de epilepsia en el contexto de una Encefalitis de Rasmussen. 4. Posibilidad de realización de RMC, pruebas electrofisiológicas, PET y evaluaciones neuropsicológicas. |
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E.4 | Principal exclusion criteria |
1. Concomitant illnesses that may affect patient safety or outcome such as: - Active CNS or systemic active infections - Active tumour - Active chemotherapy - Cardiac disease - Dementia or other degenerative CNS disease 2. Any condition in which catheterisation of the arterial system is contraindicated or not feasible (major behavioural disorders preventing adequate collaboration, difficult arterial access or clinically relevant coagulation parameters). 3. Any condition where therapeutic products cannot be administered (history of frequent adverse reactions or thromboembolic complications associated with blood components). 4. Refusal of the patient or family members to adequate follow-up. |
1. Enfermedades concomitantes que pueden afectar la seguridad del paciente o el resultado como: - Infecciones activas del SNC o sistémicas activas - Tumor activo - Quimioterapia activa - Enfermedad cardíaca - Demencia u otra enfermedad degenerativa del SNC 2. Cualquier condición en la que el cateterismo del sistema arterial esté contraindicado o no sea factible (importantes trastornos de comportamiento que impiden una colaboración adecuada, difícil acceso arterial o parámetros de coagulación clínicamente relevantes). 3. Cualquier condición que conlleve que no se pueden administrar productos terapéuticos (historial de frecuentes reacciones adversas o complicaciones tromboembólicas asociadas a los componentes de la sangre). 4. Negativa del paciente o familiares a un seguimiento adecuado |
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E.5 End points |
E.5.1 | Primary end point(s) |
To measure dose-limiting toxicities (DLTs, defined in the protocol as MSC infusion-related grade 3 toxicities occurring in the first 28 days of treatment). |
Medir toxicidades limitantes de dosis (TLD, definidas en el protocolo como toxicidades grado 3 relacionadas con la infusión de MSC que ocurran en los primeros 28 días de tratamiento). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To asses clinical response |
Evaluar la respuesta clínica |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
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 | No |
E.8.1.2 | Open | Yes |
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 | 1 |
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 | 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 | 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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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 | |