E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Chylomicronemia Syndrome (FCS) |
Sindrome da chilomicronemia familiare (FCS) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with hypertriglyceridemia |
Pazienti con ipertrigliceridemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020607 |
E.1.2 | Term | Hyperchylomicronemia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059183 |
E.1.2 | Term | Familial hypertriglyceridaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 evaluate the efficacy of ISIS 678354 as compared to placebo on the percent change in fasting triglycerides (TG) from Baseline |
Valutare l’efficacia di ISIS 678354 rispetto al placebo sulla variazione percentuale dei trigliceridi (TG) a digiuno rispetto al valore basale |
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E.2.2 | Secondary objectives of the trial |
• Proportion of patients who achieve > = 40% reduction in fasting TG from Baseline • Percent change in fasting apoB-48 from Baseline • Proportion of patients who achieve fasting TG < = 750 mg/dL (8.4 mmol/L) • Adjudicated acute pancreatitis event rate in patients with > = 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment • Adjudicated acute pancreatitis event rate • Proportion of patients who achieve > = 70% reduction in fasting TG from Baseline • Proportion of patients who achieve fasting TG < = 500 mg/dL (5.7 mmol/L) |
• Percentuale di pazienti che raggiungono una riduzione > = 40% nei livelli dei TG a digiuno rispetto al valore basale • Variazione percentuale nei livelli di apoB-48 a digiuno rispetto al valore basale • Percentuale di pazienti che raggiungono un valore di TG a digiuno < =750 mg/dl (8,4 mmol/l) • Tasso di eventi di pancreatite acuta convalidati in pazienti con > = 2 eventi di pancreatite acuta accertata nei 5 anni precedenti l’arruolamento • Tasso di eventi di pancreatite acuta convalidati • Percentuale di pazienti che raggiungono una riduzione > = 70% nei livelli dei TG a digiuno rispetto al valore basale • Percentuale di pazienti che raggiungono un valore di TG a digiuno < = 500 mg/dl (5,7 mmol/l) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A diagnosis of genetically confirmed Familial Chylomicronemia Syndrome (type 1 Hyperlipoproteinemia) • Fasting TG > = 880 mg/dL (10 mmol/L) at Screening • History of pancreatitis. Patients without a documented history of pancreatitis are also eligible but their enrollment will be capped at 20% |
• Una diagnosi di sindrome da chilomicronemia familiare geneticamente confermata (iperlipoproteinemia di tipo 1) • livelli di TG a digiuno > = 880 mg/dL (10 mmol/L) allo screening • Anamnesi di pancreatite. Sono idonei anche i pazienti privi di un’anamnesi registrata di pancreatite, ma il loro arruolamento sarà limitato al 20% |
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E.4 | Principal exclusion criteria |
• Acute coronary syndrome within 6 months of Screening • Major surgery within 3 months of Screening • Active pancreatitis within 4 weeks of Screening • Platelet count < 100K/mm3 at Screening or Qualification • Have any other conditions, which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study |
• sindrome coronarica acuta entro 6 mesi dallo screening • intervento di chirurgia maggiore entro 3 mesi dallo screening • pancreatite acuta nelle 4 settimane precedenti lo screening • conta piastrinica <100K / mm3 allo screening o alla qualificazione • presenza di qualsiasi altra condizione che, nell’opinione dello sperimentatore, potrebbe rendere il paziente inadatto all’inclusione o potrebbe interferire con la partecipazione del paziente allo studio o con il completamento di quest’ultimo |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the percent change in fasting TG from Baseline at 6 months (average of Weeks 23, 25 and 27) compared to placebo |
L’endpoint primario è la variazione percentuale nei livelli di TG a digiuno dal valore basale a 6 mesi (media delle Settimane 23, 25 e 27) rispetto al placebo |
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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) |
Secondary endpoints include the following: • Percent change in fasting TG from Baseline at 12 months (average of Week 51 and Week 53) compared to placebo • Proportion of patients who achieve > = 40% reduction in fasting TG from baseline at 6 months compared to placebo • Percent change in fasting apoB-48 from Bbaseline at 6 months compared to placebo • Proportion of patients who achieve fasting TG < = 750 mg/dL at 6 months compared to placebo • Proportion of patients who achieve fasting TG < = 500 mg/dL at 6 months compared to placebo • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53) compared to placebo, in patients with > = 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53) compared to placebo • Proportion of patients who achieve > = 70% reduction in fasting TG from Baseline at 6 months compared to placebo |
Gli endpoint secondari includono i seguenti: • Variazione percentuale nei livelli di TG a digiuno dal valore basale a 12 mesi (media delle Settimane 51 e 53) rispetto al placebo • Percentuale di pazienti che raggiungono una riduzione > = 40% nei livelli dei TG a digiuno dal valore basale a 6 mesi rispetto al placebo • Variazione percentuale nei livelli di apoB-48 a digiuno dal valore basale a 6 mesi rispetto al placebo • Percentuale di pazienti che raggiungono livelli di TG a digiuno < =750 mg/dl a 6 mesi rispetto al placebo • Percentuale di pazienti che raggiungono livelli di TG a digiuno < =500 mg/dl a 6 mesi rispetto al placebo • Tasso di eventi di pancreatite acuta convalidati durante il periodo di trattamento (dalla Settimana 1 alla Settimana 53) rispetto al placebo, in pazienti con > = 2 eventi di pancreatite acuta convalidati nei 5 anni precedenti l’arruolamento • Tasso di eventi di pancreatite acuta convalidati durante il periodo di trattamento (dalla Settimana 1 alla Settimana 53) rispetto al placebo • Percentuale di pazienti che raggiungono una riduzione > =70% nei livelli dei TG a digiuno dal valore basale a 6 mesi rispetto al placebo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 months and 12 months |
6 mesi e 12 mesi |
|
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 | No |
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 | 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 | 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 | Yes |
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 | 14 |
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 |
Canada |
Israel |
United States |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Portugal |
Slovakia |
Spain |
Sweden |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |