E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Hypertriglyceridemia (sHTG) |
Ipertrigliceridemia grave (SHTG) |
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E.1.1.1 | Medical condition in easily understood language |
Severe Hypertriglyceridemia (sHTG) |
Ipertrigliceridemia grave (SHTG) |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020870 |
E.1.2 | Term | Hypertriglyceridemia |
E.1.2 | System Organ Class | 100000004861 |
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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 |
The primary objective is to determine the change in Triglycerides (TG) levels following 12 weeks of repeated Intravenous (IV) doses of evinacumab. |
L'obiettivo primario è determinare la variazione nei livelli di trigliceridi (TG) dopo 12 settimane di dosi endovenose (EV) ripetute di evinacumab. |
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E.2.2 | Secondary objectives of the trial |
- To determine the percent change from baseline in TG levels following 2 to 24 weeks of repeated IV doses of evinacumab. - To assess changes in patient reported abdominal and gastrointestinal (GI) symptoms, dietary habits, and symptom/dietary impact measures. - To assess the degree of pancreatic injury/inflammation through 18F-2- Fluoro-2-Deoxy-D glucose positron emission tomography (18F-FDG-PET) imaging and diffusion weighted-magnetic resonance imaging (DW-MRI). - To evaluate the total evinacumab and total ANGPTL3 concentrations, and anti-drug antibody (ADA) during the evinacumab treatment and follow-up periods - To evaluate the safety and tolerability of evinacumab. |
-Determinare la variazione percentuale rispetto al basale nei livelli di TG dopo 2 24 settimane di dosi EV ripetute di evinacumab. -Valutare le variazioni nei sintomi addominali e gastrointestinali (GI), nelle abitudini alimentari e nelle misure dell' impatto di sintomi/alimentazione riferiti dal paziente. -Valutare il grado di lesione/infiammazione del pancreas mediante tomografia ad emissione di positroni con 18F-2-fluoro-2-desossi-D glucosio (18F-FDG-PET) e risonanza magnetica pesata in diffusione (DW-RM). - Valutare le concentrazioni totali di evinacumab e ANGPTL3 e gli anticorpi anti-farmaco (ADA) durante i periodi di trattamento con evinacumab e di follow-up. -Valutare la sicurezza e la tollerabilità di evinacumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1-Previous documentation in the patient's medical records of a fasting serum TG measurement = o > 1000 mg/dL (11.3 mmol/L) on more than 1 occasion, and all fasting TG values = o >500 mg/dL (5.6 mmol/L) at screening 2._History of a hospitalization and diagnosis of acute pancreatitis in the past 10 years 3_A stable lipid-modifying diet and/or medication (eg, statins, niacin, omega-3 fatty acids) for at least 4 weeks (6 weeks for fibrates, 8 weeks for PCSK9 inhibitors) prior to screening 4_Body mass index (BMI) of 18-40 kg/m2
Note: other protocol defined inclusion criteria may apply |
1_Precedente documentazione nella cartella clinica del paziente di una misurazione dei valori di TG sierici a digiuno = o >1000 mg/dl (11,3 mmol/l) in più di 1 occasione e tutti i valori di TG a digiuno = o >500 mg/dl (5,6 mmol/l) allo screening 2._Anamnesi di ricovero e diagnosi di pancreatite acuta negli ultimi 10 anni. 3_Una dieta e/o un farmaco (ad es. statine, niacina, acidi grassi omega-3) modificanti il profilo lipidico stabili per almeno 4 settimane (6 settimane per i fibrati, 8 settimane per gli inibitori di PCSK9) prima dello screening 4_ Indice IMC di 18-40 kg/m2 Nota: si possono applicare altri criteri di inclusione definiti nel protocollo |
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E.4 | Principal exclusion criteria |
1_A hospital or clinic discharge diagnosis of acute pancreatitis within 12 weeks of screening 2. Lipid apheresis or plasma exchange treatment within the last 4 weeks or plans to undergo apheresis or plasma exchange during the time frame of the study 3_History of class 3/4 heart failure at any time in the past, or hospitalization for heart failure, diagnosis of a myocardial infarction, stroke, Transient ischemic attack (TIA), unstable angina, Coronary artery bypass surgery (CABG), Percutaneous coronary intervention (PCI), carotid surgery/ stenting within 3 months before the screening visit 4_History of bleeding disorders, esophageal varices, heparin induced thrombocytopenia, or contraindications to receiving heparin (eg, allergic reaction to heparin) 5_Previous treatment with Glybera® in the past 5 years or treatment with lomitapide or mipomersen in the past 6 months 6. Pregnant or breast feeding women
Note: Other protocol defined Inclusion/Exclusion criteria may apply |
1_Diagnosi alle dimissioni dalla clinica o dall’ospedale di pancreatite acuta entro 12 settimane dallo screening 2_Trattamento di aferesi lipidica o ricambio plasmatico entro le ultime 4 settimane o trattamento pianificato di aferesi o ricambio plasmatico durante l’arco temporale dello studio 3_Anamnesi di insufficienza cardiaca di classe 3/4 in qualsiasi momento in passato, o ricovero per insufficienza cardiaca, diagnosi di infarto miocardico, ictus, TIA, angina instabile, bypass aorto-coronarico (CABG), angioplastica (PCI), intervento/stenting della carotide nei 3 mesi precedenti la visita di screening 4_Anamnesi di disturbi emorragici, varici esofagee, trombocitopenia indotta da eparina o controindicazioni a ricevere eparina (ad es. reazione allergica all’eparina) 5_Precedente trattamento con Glybera® negli ultimi 5 anni o trattamento con lomitapide o mipomersen negli ultimi 6 mesi. 6_Gravidanza o allattamento. Nota bene: si possono applicare altri criteri di inclusione/esclusione definiti dal protocollo.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent lowering of TG levels from baseline following 12 weeks of repeated IV doses of evinacumab. |
Riduzione percentuale rispetto al basale dei livelli di TG dopo 12 settimane di dosi EV ripetute di evinacumab. |
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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) |
2. Percent TG lowering from baseline following 2 to 24 weeks of repeated IV doses of evinacumab 3_Changes in patient reported abdominal and GI daily symptom questionnaire. 4_Changes in patient reported daily dietary habits and impact questionnaire. 5_Degree of pancreatic injury/inflammation through 18F-2-Fluoro-2-Deoxy-D glucose positron emission tomography (18F-FDG-PET) imaging at baseline as assessed by 18F-FDG standardized uptake values SUVmax and SUVmean. 6_Change from baseline to degree of pancreatic injury/inflammation through 18F-FDG-PET imaging following 12 weeks of treatment with evinacumab as assessed by 18F-FDG standardized uptake values SUVmax and SUVmean. 7_Degree of pancreatic injury/inflammation through Diffusion Weighted-Magnetic Resonance Imaging (DW-MRI) at baseline as assessed by ADC. 8_Change from baseline to degree of pancreatic injury/inflammation through DW-MRI following 12 weeks of treatment with evinacumab as assessed by ADC. 9_Change from baseline to degree of pancreatic injury/inflammation through DW-MRI following 24 weeks of treatment with evinacumab as assessed by ADC. 10_Total evinacumab concentration in serum. 11_Total ANGPTL3 concentrations. 12_Incidence of anti-drug antibody (ADA) 13_Incidence of Treatment-emergent adverse events (TEAEs) 14_Incidence of serious adverse events (SAEs). 15_Incidence of laboratory abnormalities. |
2_Riduzione percentuale rispetto al basale dei livelli di TG dopo 2-24 settimane di dosi EV ripetute di evinacumab. 3_Variazioni nel questionario sui sintomi addominali e GI giornalieri riferiti dal paziente. 4_Variazioni nel questionario sulle abitudini alimentari giornaliere e sull¿impatto riferiti dal paziente. 5_Grado di lesione/infiammazione del pancreas valutato mediante tomografia ad emissione di positroni con 18F-2-fluoro-2-desossi-D glucosio (18F-FDG-PET) al basale, come misurato in base ai valori di captazione standardizzati (SUV) del 18F FDG SUVmax e SUVmedio. 6_Variazione rispetto al basale nel grado di lesione/infiammazione del pancreas valutato mediante 18F-FDG-PET dopo 12 settimane di trattamento con evinacumab, come misurata in base ai valori di captazione standardizzati del 18F-FDG SUVmax e SUVmedio. 7_Grado di lesione/infiammazione del pancreas valutato mediante risonanza magnetica pesata in diffusione (DW-RM) al basale, come misurato in base al coefficiente di diffusione apparente (ADC). 8_Variazione rispetto al basale nel grado di lesione/infiammazione del pancreas valutato mediante DW-RM dopo 12 settimane di trattamento con evinacumab, come misurata in base all¿ADC. 9_Variazione rispetto al basale nel grado di lesione/infiammazione del pancreas valutato mediante DW-RM dopo 24 settimane di trattamento con evinacumab, come misurata in base all¿ADC. 10_Concentrazione totale di evinacumab nel siero. 11_Concentrazioni totali di ANGPTL3. 12_Incidenza di anticorpi anti-farmaco (ADA). 13_Incidenza di eventi avversi emergenti dal trattamento (TEAE). 14_Incidenza di eventi avversi seri (SAE). 15_Incidenza di anomalie di laboratorio.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These will be assessed at various timepoints detailed in the protocol: 2. Up to 24 Weeks 3. Up to 48 Weeks. 4. Up to 48 Weeks. 5. Baseline. 6. Week 12. 7. Baseline. 8. Week 12. 9. Week 24. 10. Up to 48 Weeks. 11. Up to 48 Weeks. 12. Up to 48 Weeks. 13. Up to 48 Weeks. 14. Up to 48 Weeks. 15. Up to 48 Weeks. |
Le valutazioni avverranno in corrispondenza di time point diversi specificati nel protocollo: 2. Fino a 24 settimane 3. Fino a 48 settimane 4. Fino a 48 settimane 5. Basale 6. Settimana 12 7. Basale 8. Settimana 12 9. Settimana 24 10. Fino a 48 settimane 11. Fino a 48 settimane 12. Fino a 48 settimane 13. Fino a 48 settimane 14. Fino a 48 settimane 15. fino a 48 settimane
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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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
United States |
Italy |
United Kingdom |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 27 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 27 |