E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe hypertryglyceridemia |
Ipertrigliceridemia grave |
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E.1.1.1 | Medical condition in easily understood language |
Patients with increased amount of fat in blood |
Pazienti con aumento della quantità di grasso nel sangue |
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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 |
|
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 |
|
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 olezarsen as compared to placebo on the percent change in fasting TG from Baseline |
Valutare l’efficacia di olezarsen rispetto al placebo sulla variazione percentuale nei livelli di TG a digiuno rispetto al valore basale |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of olezarsen as compared to placebo on: 1/ Proportion of patients who achieve fasting TG < 500 mg/dL (5.65 mmol/L) 2/ Proportion of patients who achieve fasting TG < 880 mg/dL (10 mmol/L) 3/ Proportion of patients who achieve fasting TG < 1000 mg/dL (11.29 mmol/L) 4/ Adjudicated acute pancreatitis event rate in patients with = 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment 5/ Adjudicated acute pancreatitis event rate |
Valutare l’efficacia di olezarsen rispetto al placebo relativamente a: 1/ Percentuale di pazienti che raggiungono livelli di TG a digiuno < 500 mg/dl (5,65 mmol/l) 2/ Percentuale di pazienti che raggiungono livelli di TG a digiuno < 880 mg/dl (10 mmol/l) 3/ Percentuale di pazienti che raggiungono livelli di TG a digiuno < 1.000 mg/dl (11,29 mmol/l) 4/ Tasso di eventi di pancreatite acuta convalidati in pazienti con = 2 eventi di pancreatite acuta convalidata nei 5 anni precedenti l’arruolamento 5/ Tasso di eventi di pancreatite acuta convalidati |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Fasting TG = 500 mg/dL (5.65 mmol/L) at Screening and Qualification • Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.
Other protocol defined criteria will apply. |
• Livelli di TG a digiuno = 500 mg/dl (5,65 mmol/l) allo screening e qualificazione • I pazienti devono essere sottoposti a terapia ipolipemizzante conforme allo standard di cura (SOC) in base alle linee guida locali I farmaci ipolipemizzanti devono essere ottimizzati e stabilizzati per almeno 4 settimane prima dello screening, per ridurne al minimo le variazioni durante lo studio.
Verranno applicati altri criteri definiti dal protocollo. |
|
E.4 | Principal exclusion criteria |
• Hemoglobin A1c (HbA1c) = 9.5% at Screening • Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal • Total bilirubin > upper limit of normal unless due to Gilbert's syndrome • Estimated GFR < 30 mL/min/1.73 m^2
Other Protocol defined exclusion criteria will apply. |
• Emoglobina A1c (HbA1c) = 9,5% allo screening • Alanina aminotransferasi (ALT) o aspartato aminotransferasi (AST) > 3,0 volte il limite superiore dell’intervallo normale • Bilirubina totale > al limite superiore dell’intervallo normale a meno che non sia dovuta alla sindrome di Gilbert • Velocità di filtrazione glomerulare stimata (eGFR) stimata < 30 ml/min/1,73 m2
Verranno applicati altri criteri di esclusione definiti dal protocollo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the percent change in fasting TG from Baseline at Month 6 (average of Weeks 25 and 27) compared to placebo. |
L’endpoint primario è la variazione percentuale nei livelli di TG a digiuno dal valore basale al Mese 6 (media delle Settimane 25 e 27) rispetto al placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline, 6 months |
valore basale, 6 mesi |
|
E.5.2 | Secondary end point(s) |
1. Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo 2. Proportion of Participants Who Achieve Fasting TG Less Than (<) 500 milligrams per deciliter (mg/dL) (5.7 millimoles per liter [mmol/L]) at 6 and 12 Months Compared to Placebo 3. Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 880 mg/dL 4. Proportion of Participants Who Achieve Fasting TG < 1000 mg/dL (11.29 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG = 1000 mg/dL 5. Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoCIII) at 6 and 12 Months Compared to Placebo 6. Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo 7. Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo 8. Percent Change from Baseline in Fasting High-Density Lipoprotein- Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo 9. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo, in Participants with = 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment 10. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo |
1. Variazione percentuale nei livelli di TG a digiuno dal valore basale al Mese 12 (media delle Settimane 51 e 53) rispetto al placebo 2. Percentuale di pazienti che raggiungono livelli di TG a digiuno minore di (<) 500 milligrammi per decilitro (mg/dl) (5,7 mmol/l [millimoli per litro]) ai Mesi 6 e 12 rispetto al placebo 3. Percentuale di pazienti che raggiungono livelli di TG a digiuno < 880 mg/dl (10 mmol/l) ai Mesi 6 e 12 rispetto al placebo nel sottogruppo di pazienti con valore basale di TG = 880 mg/dl 4. Percentuale di pazienti che raggiungono livelli di TG a digiuno < 1.000 mg/dl (11,29 mmol/l) ai Mesi 6 e 12 rispetto al placebo nel sottogruppo di pazienti con valore basale di TG = 1.000 mg/dl 5. Variazione percentuale dal valore basale di Apolipoproteina C-III (ApoCIII) a digiuno ai Mesi 6 e 12 rispetto al placebo 6. Variazione percentuale dal valore basale di colesterolo legato a lipoproteine a bassissima densità (VLDL-C) a digiuno ai Mesi 6 e 12 rispetto al placebo 7. Variazione percentuale dal valore basale dicolesterolo legato a lipoproteine non ad alta densità (Non-HDL-C) a digiuno ai Mesi 6 e 12 rispetto al placebo 8. Variazione percentuale dal valore basale di colesterolo legato a lipoproteine ad alta densità (HDL-C) a digiuno ai Mesi 6 e 12 rispetto al placebo 9. Tasso di eventi di pancreatite acuta convalidati durante il periodo di trattamento rispetto al placebo, in pazienti con = 2 eventi di pancreatite acuta convalidata nei 5 anni precedenti l’arruolamento 10. Tasso di eventi di pancreatite acuta convalidati durante il periodo di trattamento rispetto al placebo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2) Baseline and Month 12 3, 4) Month 6 and 12 5, 6, 7, 8) Baseline, Month 6 and 12 9, 10) Week 1 through Week 53 |
1, 2) valore basale e Mese 12 3, 4) Mesi 6 e 12 5, 6, 7, 8) Valore basale, Mese 6 e Mese 12 9, 10) Dalla settimana 1 alla settimana 53 |
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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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 57 |
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 |
Canada |
Israel |
New Zealand |
South Africa |
United States |
Finland |
France |
Poland |
Sweden |
Bulgaria |
Netherlands |
Spain |
Czechia |
Germany |
Italy |
Denmark |
Hungary |
Norway |
Portugal |
Slovakia |
Turkey |
United Kingdom |
|
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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|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |