E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypercholesterolaemia |
Hipercolesterolemia |
|
E.1.1.1 | Medical condition in easily understood language |
Hypercholesterolaemia |
Hipercolesterolemia |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020603 |
E.1.2 | Term | Hypercholesterolaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition 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 |
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) patients age of 8 to 17 years, with LDL-C ≥130 mg/dL (3.37 mmol/L) on optimal stable daily dose of statin therapy +/- other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at least 4 weeks prior to the screening period. |
Evaluar el efecto de alirocumab administrado cada 2 semanas (C2S) o cada 4 semanas (C4S) sobre los niveles de colesterol de lipoproteínas de baja densidad (C LDL) tras 8 semanas de tratamiento en pacientes con hipercolesterolemia familiar heterocigótica (HFhe) con edades comprendidas entre 8 y 17 años, con niveles de C LDL ≥130 mg/dl (3,37 mmol/l) que estén recibiendo una dosis diaria estable óptima de tratamiento con estatinas ± otros tratamientos modificadores de lípidos (TML) o una dosis estable de TML sin estatinas en caso de intolerancia a las estatinas, durante al menos 4 semanas antes del periodo de selección. |
|
E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of alirocumab. -To evaluate the pharmacokinetics profile of alirocumab. -To evaluate the effects of alirocumab on other lipid parameters. |
-Evaluar la seguridad y la tolerabilidad de alirocumab. -Evaluar el perfil farmacocinético de alirocumab. -Evaluar los efectos de alirocumab sobre los niveles de otros parámetros lipídicos |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Children and adolescent male and female patients age of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female patients aged ≥12 and ≤17 years at the time of signed informed consent. -Patients with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria. -Patients treated with optimal dose of statin +/- other LMT(s) or non-statin LMT(s) if statin intolerant at stable dose for at least 4 weeks prior to screening visit (Week -2). -Patients with calculated LDL-C greater than or equal to 130 mg/dL (≥3.37 mmol/L) at the screening visit (Week -2). -Patients with body weight greater than or equal to 25kg. -Patients age of 8 to 9 years to be at Tanner stage 1 and patients age of 10 to 17 years to be at least at Tanner stage 2 in their development. -A signed informed consent indicating parental permission with or without patient assent. |
I 01. Niños y adolescentes de ambos sexos con edades comprendidas entre 8 y 17 años en el momento de la firma del consentimiento informado. I 02. Pacientes con un diagnóstico de hipercolesterolemia familiar heterocigótica (HFhe) por genotipado o criterios clínicos. I 03. Pacientes tratados con una dosis óptima de estatinas con o sin otro(s) TML o TML sin estatinas en caso de intolerancia a las estatinas a una dosis estable durante al menos 4 semanas antes de la visita de selección (Semana -2). I 04. Pacientes con C LDL calculado mayor o igual a 130 mg/dl (≥3,37 mmol/l) en la visita de selección (Semana -2). I 05. Pacientes con peso corporal superior o igual a 25 kg. I 06. Pacientes con edades comprendidas entre 8 y 9 años con estadio 1 de Tanner y pacientes con edades comprendidas entre 10 y 17 años al menos con estadio 2 de Tanner en su desarrollo. I 07. Firma de consentimiento informado indicando el permiso paterno con o sin el asentimiento del paciente, dependiendo de la capacidad de comprensión basada en el grado de madurez. |
|
E.4 | Principal exclusion criteria |
-Patient with secondary hyperlipidemia. -Diagnosis of homozygous familial hypercholesterolemia. -Patient who has received lipid apheresis treatment within 2 months prior to the screening period, or has plans to receive it during the study. -Known history of type 1 or type 2 diabetes mellitus. -Known history of thyroid disease. -Known history of hypertension. -Fasting triglycerides >350 mg/dL (3.95 mmol/L). -Severe renal impairment (ie, estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m^2. -Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN). -Creatinine phosphokinase (CPK) >3 x ULN. |
• Paciente con hiperlipidemia secundaria. • Diagnóstico de hipercolesterolemia familiar homocigótica. • Paciente que ha recibido tratamiento de aféresis de lípidos en los 2 meses previos al periodo de selección, o que tiene previsto recibirlo durante el estudio. • Antecedentes conocidos de diabetes mellitus tipo 1 o tipo 2. • Antecedentes conocidos de enfermedad tiroidea. • Antecedentes conocidos de hipertensión. • Triglicéridos en ayunas >350 mg/dl (3,95 mmol/l) en la visita de selección (Semana -2). • Insuficiencia renal grave (es decir, TFGe <30 ml/min/1,73 m2 en la visita de selección [Semana -2]). • ALT o AST >2 x LSN (se permite 1 repetición de la analítica). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in calculated LDL-C |
Cambio porcentual en el C LDL calculado |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to Week 8 |
Desde el momento basal hasta la Semana 8. |
|
E.5.2 | Secondary end point(s) |
a) Absolute change in calculated LDL-C b) Percentage of participants achieving a calculated LDL-C level lower than 130 mg/dL (3.37 mmol/L) c) Percentage of participants achieving a calculated LDL-C level lower than 110 mg/dL (2.84 mmol/L) d) Percent change in Apolipoprotein B (Apo B) e) Percent change in non-high density lipoprotein cholesterol (non HDL-C) f) Percent change in Total-C g) Percent change in Lipoprotein (a) (Lp[a]) h) Percent change in triglycerides (TG) I) Percent change in HDL-C l) Percent change in Apo A-1 m) Absolute change in Apo B n) Absolute change in non-HDL-C o) Absolute change in Total-C p) Absolute change in Lp(a) q) Absolute change in TG r) Absolute change in HDL-C s) Absolute change in Apo A-1 t) Absolute change in ratio Apo B/Apo A-1 |
a) Cambio absoluto en el C-LDL calculado b) Porcentaje de participantes que alcanzaron un nivel de LDL-C por debajo de 130 mg / dl (3,37 mmol / L) c) Porcentaje de participantes que alcanzaron un nivel de LDL-C inferior a 110 mg / dl (2,84 mmol / L) d) El porcentaje de cambio en la apolipoproteína B (Apo B) e) El porcentaje de cambio en las lipoproteínas de colesterol de no-alta densidad (no HDL-C) f) Cambio porcentual en el total-C g) Cambio porcentual en el lipoproteína (a) (Lp [a]) h) El porcentaje de cambio en los triglicéridos (TG) I) El porcentaje de cambio en el HDL-C |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) From baseline to Week 8 b), c) : At week 8 d), e), f), g) h), I), l), m), n), o), p), q), r), s), t) : From baseline to Week 8 |
a) Desde el inicio hasta la semana 8 b), c): En la semana 8 d), e), f), g), h), I), l), m), n), o), p), q), r), s), t): Desde el inicio hasta la semana 8 |
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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 | 6 |
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 | 11 |
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 |
Australia |
Canada |
Israel |
Norway |
Russian Federation |
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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
|
LVLS |
Última visita del último paciente |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |