E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Monotherapy for the treatment of infantile spasms (IS) in infants and children 2 months to 24 months of age |
Monoterapia para el tratamiento de espasmos infantiles (EI) en lactantes y niños de 2 a 24 meses de edad, ambos inclusive |
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E.1.1.1 | Medical condition in easily understood language |
Infantile Spasms |
Espasmos infantiles |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021750 |
E.1.2 | Term | Infantile spasms |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021751 |
E.1.2 | Term | Infantile spasms, with intractable epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021752 |
E.1.2 | Term | Infantile spasms, without mention of intractable epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 objective of this study is to evaluate the efficacy of AMZ002 in patients who are 2 months to 24 months of age, inclusive, with newly diagnosed IS, compared to vigabatrin. |
El objetivo principal de este estudio es evaluar la eficacia de AMZ002 en pacientes de 2 a 24 meses de edad, inclusive, con EI de diagnóstico reciente, en comparación con vigabatrina. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are the following: • To evaluate the safety of AMZ002 in patients who are 2 months to 24 months of age, inclusive, with newly diagnosed IS; and • To evaluate the pharmacodynamics (PD) of AMZ002 in patients who are 2 months to 24 months of age, inclusive, with newly diagnosed IS. |
Los objetivos secundarios de este estudio son los siguientes: • Evaluar la seguridad de AMZ002 en pacientes de 2 a 24 meses de edad, ambos inclusive, con EI de diagnóstico reciente; y • Evaluar la farmacodinámica (FD) de AMZ002 en pacientes de 2 a 24 meses de edad, ambos inclusive, con EI de diagnóstico reciente. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria Patients who meet all of the following criteria will be eligible to participate in the study: 1. Patient is male or female and is 2 months to 24 months of age, inclusive; 2. Patient has been diagnosed with IS within 6 weeks prior to Screening. Diagnostic criteria include both clinical spasms and an electroencephalogram (EEG) pattern consistent with hypsarrhythmia or significant abnormality compatible with IS; NOTE: If a video EEG is performed at the clinical site within 48 hours prior to the patient’s parent/guardian providing written informed consent, and it meets the criteria, this video EEG may be used as the screening/baseline EEG for the study. 3. Patient has normal renal function as defined by an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2, calculated as eGFR = 0.413 × (height [cm] / serum creatinine [mg/dL]); 4. Patient’s legally authorized representative (ie, parent or guardian) must provide written informed consent obtained per Institutional Review Board policy and requirements, consisten with the International Council for Harmonisation; and 5. Patient’s parent/guardian is able to understand and willing to comply with study procedures and restrictions. |
Los pacientes que cumplan todos los criterios siguientes serán aptos para participar en el estudio: 1. El paciente es hombre o mujer y tiene entre 2 y 24 meses de edad, inclusive. 2. El paciente ha sido diagnosticado con EI en las 6 semanas anteriores a la selección. Los criterios diagnósticos incluyen tanto espasmos clínicos como un patrón electroencefalográfico (EEG) coherente con hipsarritmia o anomalía significativa compatible con EI; NOTA: si se realiza un vídeo-EEG en el centro clínico en las 48 horas anteriores a que el progenitor/tutor del paciente proporcione el consentimiento informado por escrito y cumple los criterios, este vídeo-EEG puede utilizarse como EEG de selección/inicio para el estudio. 3. El paciente tiene una función renal normal definida por una tasa de filtración glomerular estimada (TFGe) >60 ml/min/1,73 m2, calculada como TFGe = 0,413 × (altura [cm]/creatinina sérica [mg/dl]); 4. El representante legal del paciente (es decir, el progenitor o tutor) debe proporcionar el consentimiento informado por escrito obtenido según la política y los requisitos del Comité de Ética de la Investigación con medicamentos, de conformidad con la Conferencia Internacional sobre la Armonización; y 5. El progenitor/tutor del paciente es capaz de comprender y está dispuesto a cumplir con los procedimientos y restricciones del estudio. |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from participation in the study: 1. Patient has been diagnosed with tuberous sclerosis; 2. Patient has acute illness considered clinically significant by the Investigator within 30 days prior to Screening; 3. Patient has a diagnosis of recent systemic fungal infection; history of ocular herpes simplex; history of or current peptic ulcer; uncontrolled hypertension or congestive heart failure; or any other condition that would be significantly impacted by the study drug; 4. Patient has a preplanned surgery or procedure(s) that would interfere with the conduct of the study; 5. Patient has received any prior treatment for IS; 6. Patient has been previously treated with adrenocorticotropic hormone (ACTH), corticosteroids, or vigabatrin for seizures; 7. Patient has been previously treated with a course of corticosteroids for an indication other than seizures within 30 days prior to Screening; 8. Patient has a known or suspected allergy to ACTH or vigabatrin or any component of AMZ002 or vigabatrin; 9. Patient has used any other investigational drug within 30 days or 5 half-lives prior to the first dose of AMZ002 or vigabatrin (whichever is longer); 10. Patient’s parent/guardian is unable to provide written informed consent and/or to complete the daily diary; or 11. Patient has any other disease, condition, or therapy that, in the opinion of the Investigator, might compromise safety or compliance, preclude the patient from successfully completing the study, or interfere with the interpretation of the results. |
Los pacientes que cumplan alguno de los criterios siguientes quedarán excluidos de participar en el estudio: 1. El paciente ha sido diagnosticado de esclerosis tuberosa; 2. El paciente tiene una enfermedad aguda que el investigador considera clínicamente significativa en los 30 días anteriores a la selección; 3. El paciente tiene un diagnóstico de infección fúngica sistémica reciente; antecedentes de herpes simple ocular; antecedentes o presencia de úlcera péptica; hipertensión no controlada o insuficiencia cardíaca congestiva; o cualquier otra afección que se vería significativamente afectada por el fármaco del estudio; 4. El paciente se somete a una intervención quirúrgica o a procedimientos planificados previamente que interferirían con la realización del estudio; 5. El paciente ha recibido cualquier tratamiento previo para los EI; 6. El paciente ha sido tratado previamente con hormona adrenocorticotrópica (ACTH), corticosteroides o vigabatrina para las convulsiones; 7. El paciente ha sido tratado previamente con un ciclo de corticosteroides para una indicación distinta de convulsiones en los 30 días anteriores a la selección; 8. El paciente tiene una alergia conocida o sospechada a ACTH o vigabatrina o a cualquier componente de AMZ002 o vigabatrina; 9. El paciente ha usado cualquier otro fármaco en investigación en los 30 días o 5 semividas anteriores a la primera dosis de AMZ002 o vigabatrina (lo que sea más largo); 10. El progenitor/tutor del paciente no puede proporcionar el consentimiento informado por escrito o cumplimentar el diario todos los días; o 11. El paciente tiene cualquier otra enfermedad, afección o tratamiento que, en opinión del investigador, podría comprometer la seguridad o el cumplimiento, impedir que el paciente complete el estudio con éxito o interferir con la interpretación de los resultados. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints The co-primary efficacy endpoints are the following: • Proportion of patients with absence of clinical spasms at Day 14, as indicated by video EEG; and • Proportion of patients with resolution of hypsarrhythmia or significant abnormality compatible with IS at Day 14, as indicated by video EEG. Absence of clinical spasms and resolution of hypsarrhythmia or significant abnormality compatible with IS will be determined by an independent, blinded, and central EEG reader. |
Criterios de valoración principales de la eficacia: Los criterios de valoración coprincipales de la eficacia son los siguientes: • Proporción de pacientes con ausencia de espasmos clínicos en el día 14, según lo indicado por el vídeo-EEG; y • Proporción de pacientes con resolución de la hipsarritmia o anomalía significativa compatible con EI en el día 14, según lo indicado por el vídeo-EEG. La ausencia de espasmos clínicos y la resolución de la hipsarritmia o las anomalías significativas compatibles con EI la determinará un lector de EEG central, enmascarado e independiente. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Day 14, as indicated by video EEG -Absence of clinical spasms and resolution of hypsarrhythmia |
-Dia 14, según lo indicado por el vídeo-EEG. -Ausencia de espasmos clínicos y la resolución de la hipsarritmia. |
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E.5.2 | Secondary end point(s) |
Exploratory Efficacy Endpoints The exploratory efficacy endpoints are the following, for patients randomized to the vigabatrin group who are non-responders at Day 14 and then choose to switch to AMZ002 treatment: • Proportion of patients with absence of clinical spasms after 14 days of AMZ002 treatment, as indicated by the parent/guardian diary; and • Proportion of patients with resolution of hypsarrhythmia or significant abnormality compatible with IS after 14 days of AMZ002 treatment, as indicated by video EEG. |
Criterios de valoración exploratorios de la eficacia Los criterios de valoración exploratorios de la eficacia son los siguientes para los pacientes aleatorizados al grupo de vigabatrina que no responden el día 14 y que luego optan por cambiar al tratamiento con AMZ002: • Proporción de pacientes con ausencia de espasmos clínicos después de 14 días de tratamiento con AMZ002, según lo indicado en el diario del progenitor/tutor; y • Proporción de pacientes con resolución de la hipsarritmia o anomalía significativa compatible con EI después de 14 días de tratamiento con AMZ002, según lo indicado por el vídeo-EEG. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-patients randomized to the vigabatrin group who are non-responders at Day 14 -Proportion of patients with absence of clinical spasms after 14 days of AMZ002 treatment - Proportion of patients with resolution of hypsarrhythmia or significant abnormality compatible with IS after 14 days of AMZ002 treatment |
• Pacientes aleatorizados al grupo de vigabatrina que no responden el día 14. • Proporción de pacientes con ausencia de espasmos clínicos después de 14 días de tratamiento con AMZ002. • Proporción de pacientes con resolución de la hipsarritmia o anomalía significativa compatible con EI después de 14 días de tratamiento con AMZ002. |
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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 | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
immunogenicity |
inmunogenicidad |
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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 | No |
E.8.1.1 | Randomised | Yes |
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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
United States |
Poland |
Spain |
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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
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The end of the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last patient in the study. |
El final del estudio ("finalización del estudio") se define como la fecha de la última visita/evaluación especificada en el protocolo (incluido el contacto telefónico) para el último paciente del estudio. |
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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 | 2 |
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 | 2 |