E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Upper limb spasticity in children |
Espasticidad de la extremidad superior en niños |
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E.1.1.1 | Medical condition in easily understood language |
Upper limb spasticity (altered skeletal muscle performance) in children |
Espasticidad del miembro superior (alteracion del funcionamiento del musculo esqueletico) en niños |
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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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048970 |
E.1.2 | Term | Arm spasticity |
E.1.2 | System Organ Class | 100000004852 |
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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 |
The primary study objective is to assess the efficacy of two doses of Dysport (8 U/kg and 16 U/kg) compared to Dysport 2 U/kg used in the treatment of upper limb spasticity in children with CP following a single treatment. |
El objetivo principal del estudio es evaluar la eficacia de dos dosis de Dysport (8 unidades U/kg y 16 U/kg), en comparacion con Dysport 2 U/kg, en el tratamiento de la espasticidad de las extremidades superiores en niños con paralisis cerebral (PC) despues de un unico tratamiento. |
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E.2.2 | Secondary objectives of the trial |
The secondary study objective is to assess the long term safety of multiple treatments of Dysport used in this study population.
The tertiary study objectives will evaluate the long term efficacy of Dysport, its effect on pain in the study limb and quality of life (QoL) following multiple treatments. |
El objetivo secundario del estudio es evaluar la seguridad a largo plazo de multiples tratamientos con Dysport en la poblacion del estudio.
Los objetivos terciarios del estudio evaluaran la eficacia a largo plazo de Dysport, su efecto sobre el dolor de la extremidad evaluada en el estudio y la calidad de vida (CdV) despues de multiples tratamientos. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) Signed informed consent obtained from the child?s parent(s)/guardian(s) and, if applicable, a signed assent from the child. (2) Be from 2 to 17 years of age, inclusive. (3) Body weight of 10 kg or more at the baseline visit. (4) Have a diagnosis of CP, as defined by Rosenbaum. (5) Have increased muscle tone/spasticity in at least one upper limb. (6) Have a MAS score ?2 in the upper limb primary targeted muscle group (elbow flexors or wrist flexors) of the study limb (the limb to be injected in the first treatment) at the baseline visit. (7) Be classified as Gross Motor Function Classification System Level 1 to 4. (8) If undergoing therapy, such as physiotherapy, occupational therapy, or use of splints and/or orthoses, therapy must have been initiated at least 30 days prior to the baseline visit and agreed to continue the therapy throughout the study and at the minimum, up to Week 16 following the first treatment administration. |
(1) Consentimiento informado firmado de los padres/tutores del menor y, si procede, el asentimiento firmado del propio menor. (2) Edad de 2 a 17 años, ambos inclusive. (3) Peso corporal de 10 kg o más en la visita basal. (4) Diagnostico de PC, segun los criterios de Rosenbaum. (5) Hipertonia muscular/espasticidad como minimo en una extremidad superior. (6) Puntuacion MAS ?2 en la visita basal para el grupo muscular principal de referencia de la extremidad superior (flexores del codo o flexores de la muñeca) evaluada en el estudio (la extremidad que recibira la inyección en el primer tratamiento). (7) Nivel 1 a 4 en la escala GMFCS. (8) Si el sujeto recibe algun tipo de terapia, como fisioterapia, terapia ocupacional o uso de ferulas u ortesis, el mismo debera haberse instaurado como minimo 30 dias antes de la visita basal y tendra que acordarse la continuacion de dicha terapia durante todo el estudio y al menos hasta la semana 16 despues de la primera administracion del tratamiento. |
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E.4 | Principal exclusion criteria |
(1) Fixed myocontracture in the primary targeted muscle group (elbow flexors or wrist flexors) of the study limb defined as having an available range of motion angle of <40°, regardless of the starting and finishing angles, measured at the Tardieu Scale (TS) slow (XV1) speed at the baseline visit. (Available range for wrist flexors should be measured without holding the fingers and allowing free finger flexion). (2) Subjects likely to be treated with BTX in the lower limb(s) and/or the nonstudy upper limb before Treatment 2 of the study. (3) Inadequate washout from previous BTX injection of any serotype for any condition: ? Within 6 months prior to the baseline visit in the study limb, or ? Within 3 months prior to the baseline visit in any other part of the body. (4) Subjects who require BTX treatment in a single muscle group in the study limb in Treatment 1. (5) Severe athetoid or dystonic movements in the study limb. (6) Previous or planned surgery for spasticity in the primary targeted muscle group(s) of the study limb. (7) Previous injection of alcohol and/or phenol within 1 year prior to the baseline visit affecting the study limb wrist flexors and/or elbow flexors selected for injection in Treatment 1. (8) Treatment with any drug that interferes either directly or indirectly with neuromuscular function (e.g. aminoglycoside antibiotics) or neuroblocking agents used during surgery (e.g. curare) within the last 30 days prior to study treatment. (9) Are pregnant and/or lactating. (10) Female subjects not willing to use contraceptive measures throughout the course of the study if postpubertal and sexually active. (11) Inability or unwillingness to comply with the protocol. (12) Subjects with any clinical (or sub-clinical) evidence of marked defective neuromuscular transmission (e.g. Lambert-Eaton syndrome or myasthenia gravis) or persistent clinically significant neuromuscular disorders. (13) Known sensitivity to BTX or to any of the components in the formulation or allergy to cow?s milk protein. (14) An infection at the injection site(s). (15) Previous rhizotomy less than 6 months prior to the baseline visit or rhizotomy planned/anticipated during the course of the study. (16) Subjects treated or likely to be treated with intrathecal baclofen within 30 days prior to the baseline visit or during the course of the study. (17) Treatment with a new investigational drug within 30 days prior to the baseline visit or scheduled to receive such a drug during the course of the study. (18) Subjects with a history of aspiration or conditions which put them at risk of aspiration, such as severe dysphagia. (19) Concurrent or history of frequent lower respiratory tract infections, aspiration pneumonia, or, as judged by the Investigator, has compromised respiratory function. (20) Any known medical condition, laboratory or diagnostic procedure finding, which might compromise compliance with the objectives and procedures of this protocol or preclude administration of botulinum toxin type A (BTX-A), as judged by the Investigator. (21) Any uncontrolled clinically significant medical condition other than CP. |
(1) Contractura muscular fija en el grupo muscular principal de referencia (flexores del codo o flexores de la muñeca) de la extremidad evaluada en el estudio, definida como un angulo de amplitud de movimiento <40°, independientemente de los angulos inicial y final, determinado a velocidad lenta (XV1) segun la escala Tardieu en la visita basal. (El intervalo de los flexores de la muñeca debera medirse sin sujetar los dedos y permitiendo la flexion libre de los mismos). (2) Sujetos que precisen tratamiento con BTX en las extremidades inferiores y/o en la extremidad superior no evaluada en el estudio antes del Tratamiento 2. (3) Periodo de lavado insuficiente de una inyeccion previa de BTX de cualquier serotipo utilizada para cualquier trastorno: ?En los 6 meses previos a la visita basal en la extremidad evaluada en el estudio o ?En los 3 meses previos a la visita basal en cualquier otra parte del cuerpo. (4) Sujetos que precisen en el Tratamiento 1 BTX en un solo grupo muscular de la extremidad evaluada en el estudio. (5) Movimientos atetoides o distonicos intensos en la extremidad evaluada en el estudio. (6) Intervencion quirurgica previa o programada por espasticidad en el grupo muscular principal de referencia de la extremidad evaluada en el estudio. (7) Inyección de alcohol y/o fenol en el año previo a la visita basal en los musculos flexores de la muñeca y/o del codo de la extremidad evaluada en el estudio elegidos para ser inyectados en el Tratamiento 1. (8) Tratamiento con cualquier farmaco que afecte directa o indirectamente a la funcion neuromuscular (p. ej., antibioticos aminoglucosidos) o uso de neurobloqueantes durante una intervención quirurgica (p. ej., curare) en los 30 dias previos al tratamiento del estudio. (9) Embarazo y/o lactancia. (10) Pacientes de sexo femenino que no deseen utilizar medidas anticonceptivas durante el transcurso del estudio si son pospuberales y sexualmente activas. (11) Incapacidad o poca disposicion para cumplir el protocolo. (12) Sujetos con evidencia clinica (o subclinica) de transmision neuromuscular defectuosa marcada (p. ej., sindrome de Lambert-Eaton o miastenia grave) o con trastornos neuromusculares persistentes clinicamente significativos. (13) Sensibilidad conocida a BTX o a alguno de los componentes de la formulacion o alergia a la proteina de la leche de vaca. (14) Infeccion en el punto de inyeccion. (15) Rizotomia en los 6 meses previos a la visita basal o programada/anticipada durante el transcurso del estudio. (16) Sujetos tratados con baclofeno intratecal en los 30 dias previos a la visita basal o con probabilidad de ser tratados durante el transcurso del estudio. (17) Tratamiento con un nuevo farmaco en investigacion en los 30 días previos a la visita basal o prevision de tal tratamiento durante el transcurso del estudio. (18) Sujetos con antecedentes de aspiracion u otro trastorno que suponga un riesgo de aspiracion, como disfagia. (19) Presencia o antecedente de infecciones frecuentes de las vias respiratorias inferiores, neumonia por aspiracion o que, a juicio del investigador, pueda afectar la funcion respiratoria. (20) Cualquier enfermedad conocida o resultados analiticos o de un procedimiento diagnostico que, a juicio del investigador, puedan poner en peligro el cumplimiento de los objetivos y los procedimientos de este protocolo o impedir la administracion de BTX-A. (21) Cualquier condicion medica no controlada clinicamente significativa, a excepcion de la PC. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Mean change from Baseline to Treatment 1, Week 6 in MAS score in the Treatment 1 primary targeted muscle group (elbow flexors or wrist flexors). |
Objetivo principal de eficacia: Cambio medio de la puntuacion MAS en el grupo muscular principal de referencia para el Tratamiento 1 (flexores del codo o de la muñeca) entre la visita basal y la semana 6 del Tratamiento 1. |
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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) |
Mean PGA score at Treatment 1, Week 6. Mean GAS score at Treatment 1, Week 6. |
Puntuacion PGA media en la semana 6 del Tratamiento 1. Puntuacion GAS media en la semana 6 del Tratamiento 1. |
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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 | 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 | 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) | No |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
dos dosis de Dysport (8 U/Kg y 16 U/Kg) frente a Dysport 2 U/Kg |
two doses of Dysport (8 units (U)/kg and 16 U/kg) compared to Dysport 2 U/kg |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Bulgaria |
France |
Portugal |
Australia |
Brazil |
Chile |
Colombia |
Czech Republic |
Georgia |
Lithuania |
Spain |
Israel |
Mexico |
Poland |
Russian Federation |
South Africa |
Turkey |
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 visit last subject |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |