E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypercholesterolemia |
Ipercolesterolemia |
|
E.1.1.1 | Medical condition in easily understood language |
Elevated levels of 'bad' cholesterol |
Elevati livelli di colesterolo cattivo |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057100 |
E.1.2 | Term | Homozygous familial hypercholesterolaemia |
E.1.2 | System Organ Class | 100000004850 |
|
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 | 10057099 |
E.1.2 | Term | Heterozygous familial hypercholesterolaemia |
E.1.2 | System Organ Class | 100000004850 |
|
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 |
To describe the safety and tolerability of 80 weeks of SC evolocumab when added to
standard of care in pediatric subjects 10 to 17 years of age with HeFH or HoFH. |
descrivere la sicurezza e la tollerabilit¿ di 80 settimane di trattamento con evolocumab sc, in aggiunta alla terapia standard, in soggetti pediatrici dai 10 ai 17 anni di et¿ con HeFH o HoFH |
|
E.2.2 | Secondary objectives of the trial |
To describe percent change and change from baseline in LDL-C, and on percent change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, and ApoB/Apolipoprotein A-1 (ApoA1) ratio. |
Descrivere la variazione percentuale e la variazione dal basale dei livelli di C-LDL, la variazione percentuale dal basale dei livelli di colesterolo legato alle lipoproteine non ad alta densit¿ (C-non HDL), apolipoproteina B (ApoB), rapporto colesterolo totale/C-HDL, e rapporto ApoB/apolipoproteina A-1 (ApoA1). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with HeFH: -Completed Study 20120123 while still on assigned investigational product. Subjects with HoFH: -Male or female, = 10 to = 17 years of age at time of enrollment -Diagnosis of HoFH by genetic confirmation or a clinical diagnosis based on a history of an untreated LDL cholesterol concentration > 500 mg/dL (13 mmol/L) together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents. All subjects: - Subject must be on a low-fat diet and receiving background lipid-lowering therapy -Lipid-lowering therapy, including statin dose, must be unchanged for = 4 weeks prior to LDL-C screening; fibrates must be stable for at least 6 weeks prior to screening. |
Soggetti HeFH: - hanno completato lo studio 20120123 mentre ricevono ancora il trattamento sperimentale. Soggetti HoFH: -femmine o maschi di età compresa tra 10 e 17 anni al momento dell'arruolamento - Diagnosi di HoFH da conferma genetica o diagnosi clinica sulla base di una storia di colesterolo LDL non trattato con concentrazione superiore a 500 mg/dL (13 mmol/L) insieme a xanthoma prima dei 10 anni di età o evidenza di ipercolesterolemia famigliare eterozigote in entrambi i genitori. Tutti i soggetti: - devono essere a dieta povera di grassi e ricevere terapia di background per abbassamento dei lipidi - la terapia di abbassamento dei livelli di lipidi, inclusa la dose statinica, deve rimanere uguale per più di 4 settimane prima dello screening LDL-C; fibrati stabili per almeno 6 settimane prima dello screening. |
|
E.4 | Principal exclusion criteria |
Subjects with HoFH: - estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2; CK > 3x ULN; AST or ALT > 3x ULN; (all screening by central laboratory); - known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction; - subject has taken a cholesterylester transfer protein (CETP) inhibitor in the last 12 months, or mipomersen or lomitapide in the last 5 months prior to LDL-C screening, or has received any therapy to inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) within 12 weeks prior to screening; - subject has a history or evidence of any other clinically significant disorder, condition or disease, or planned or expected procedure that, in the opinion of the Investigator or Amgen physician, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. The following are major exclusion criteria for all subjects: - subjects cannot be receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study; - female subjects of childbearing potential cannot be pregnant or breast feeding or planning to become pregnant or planning to breast feed and must be willing to use acceptable method(s) of effective birth control (may include true sexual abstinence) during treatment with evolocumab and for an additional 15 weeks after the end of treatment with evolocumab. |
Soggetti con HoFH: - tasso di infiltrazione glomerulare stimato (eGFR) minore di 30 ml/min/1.73m2; CK > 3x ULN; AST or ALT > 3x ULN; (tutti gli screening tramite laboratorio centralizzato); - infezione attiva conosciuta o disfunzione ematologica, renale, metabolica, gastrointestinale o endocrina maggiore; - i soggetti hanno assunto inibitore della proteina colesterilester transfer (CETP) negli ultimi 12 mesi, oppure mipomersen o lomitapide negli ultimi 5 anni precedenti lo screening LDL-C, o hanno ricevuto una terapia oer inibire la subtilisina proproteina convertasi/kexin type 9 (PCSK9) entro 12 mesi prima dello screening; - soggetti con storia o evidenza di qualsiasi altro disordine clinico significativo, condizione o patologia, o procedure previste che, a opinione dello sperimentatore, potrebbero mettere a rischio la sicurezza del paziente o interferire con la valutazione dello studio, procedure o compimento. Criteri di esclusione principali per tutti i pazienti: - soggetti che non possono ricevere trattamento con un altro device o studio clinico, o meno di 30 giorni dalla fine del trattamento con un altro device o molecola sperimentale; - soggetti femminili potenzialmente fertili non possono essere incinta o allattare o prevedere di rimanere incinta o prevedere di allattare, e devono fare uso di contracettivi accettabili per il controllo delle nascite (può includere astinenza sessuale) durante il trattamento con evolocumab e per ulteriori 15 settimane dopo la fine del trattamento.
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E.5 End points |
E.5.1 | Primary end point(s) |
Subject incidence of treatment emergent adverse events |
Incidenza delle reazioni avverse emergenti dal trattamento |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening, day 1, weeks 4, 12, 24, 36, 48, 60, 72 and 80. |
Screening, giorno 1, settimana 4, 12, 24, 36, 48, 60, 72 e 80. |
|
E.5.2 | Secondary end point(s) |
Percent change from baseline at week 80 in: - LDL-C - Non-HDL-C - ApoB - Total cholesterol/HDL-C ratio - ApoB/ApoA1 ratio ¿ Change from baseline in LDL-C at week 80 |
Variazione percentuale alla settimana 80 in: - LDL-C - Non-HDL-C - ApoB - Colesterolo totale/tasso HDL-C - Tasso ApoB/ApoA1 ¿ Scostamento dal baseline di LDL-C alla settimana 80 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline and week 80 |
Baseline e settimana 80 |
|
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 | No |
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) | 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 | No |
E.8.1.2 | Open | No |
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
| 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Information not present in EudraCT |
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 |
Brazil |
Canada |
Colombia |
New Zealand |
Russian Federation |
South Africa |
Turkey |
Austria |
Belgium |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Slovenia |
Spain |
Switzerland |
United Kingdom |
Czechia |
|
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
|
LSLV |
Ultima visita dell'ultimo soggetto |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 2 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 2 |