E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Chylomicronemia Syndrome (FCS) |
sindrome da chilomicronemia familiare |
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E.1.1.1 | Medical condition in easily understood language |
Familial Chylomicronemia Syndrome (FCS) |
sindrome da chilomicronemia familiare |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060593 |
E.1.2 | Term | Fredrickson Type I lipidemia |
E.1.2 | System Organ Class | 100000004850 |
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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 | 10017339 |
E.1.2 | Term | Fredrickson Type I lipidaemia |
E.1.2 | System Organ Class | 100000004850 |
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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 safety and efficacy of extended dosing with volanesorsen (volanesorsen sodium 300 mg) in patients with FCS |
Valutare la sicurezza e l’efficacia del dosaggio esteso con volanesorsen (volanesorsen sodio 300 mg) in pazienti affetti da FCS |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
non applicabile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Satisfactory completion of ISIS 304801-CS6 or ISIS 304801-CS16 (index studies) with an acceptable safety profile 2. History of chylomicronemia 3. A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia) 4. Fasting triglycerides ≥ 750 mg/dL (8.4 mmol/L) at Screening for the index studies |
1. Completamento soddisfacente di ISIS 304801-CS6 o ISIS 304801-CS16 (studi indice) con un profilo di sicurezza accettabile 2. Anamnesi di chilomicronemia 3. Diagnosi di sindrome da chilomicronemia familiare (iperlipoproteinemia di tipo 1) 4. TG a digiuno ≥ 750 mg/dl (8,4 mmol/l) allo screening per gli studi indice |
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E.4 | Principal exclusion criteria |
1. Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study; 2. Unwilling to comply with lifestyle requirements for the duration of the study. |
1. Presenza di qualsiasi nuova condizione o peggioramento di condizione esistente che, secondo lo Sperimentatore, potrebbe rendere il paziente inadatto all’arruolamento o potrebbe interferire con la partecipazione del paziente allo studio o con il completamento di quest’ultimo 2. Riluttanza ad adeguarsi ai requisiti dello stile di vita per la durata dello studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints: • Percent change and absolute change from baseline in fasting TG • Frequency and severity of patient reported abdominal pain during the treatment period • Percent change and change from baseline in other fasting lipid measurements including total cholesterol, non-HDL-C, apoB, HDL-C, apolipoprotein A-1 (apoA-1), VLDL-C, and LDL-C • Percent change from baseline in fasting total apolipoprotein C-III • Quality of Life questionnaires (EQ-5D, SF-36) • Adjudicated acute pancreatitis event rate • Other symptoms: eruptive xanthoma, lipemia retinalis Safety Endpoints: • Adverse events including adjudicated events of pancreatitis and MACE • Vital signs and weight • Physical examinations • Clinical laboratory tests (serum chemistry, hematology, coagulation, urinalysis) • Echocardiography • Electrocardiograms (ECGs) • Use of concomitant medications • MRIs |
Endpoint di sicurezza:
• Eventi avversi inclusi eventi di pancreatite acuta convalidati e MACE • Segni vitali e peso • Esami obiettivi • Esami clinici di laboratorio (chimica del siero, ematologia, coagulazione, analisi delle urine) • Ecocardiogramma • Elettrocardiogrammi (ECG) • Uso di terapie concomitanti • RMI
Endpoint di efficacia: • Variazione in percentuale e variazione assoluta dal basale dei TG a digiuno • Frequenza e gravità del dolore addominale riferito dal paziente durante il periodo di trattamento • Variazione in percentuale e variazione dal basale di altre misurazioni dei lipidi a digiuno incluso colesterolo totale, colesterolo delle lipoproteine non ad alta densità (non High-Density Lipoprotein Cholesterol, non-HDL-C), apolipoproteina B [apoB], colesterolo delle lipoproteine ad alta densità (High-Density Lipoprotein-Cholesterol, HDL-C), apolipoproteina A-1 [apoA-1], colesterolo delle lipoproteine a bassissima densità (Very Low-Density Lipoprotein Cholesterol, VLDL-C) e colesterolo delle lipoproteine a bassa densità (Low-Density Lipoprotein Cholesterol, LDL-C) • Variazione in percentuale dal basale dell’apolipoproteina C-III (apoC-III) totale a digiuno • Questionari sulla qualità della vita (EQ-5D, SF-36) • Tasso di eventi di pancreatite acuta convalidati • Altri sintomi: xantoma eruttivo, lipemia retinica |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Fasting lipid measurements: Month 3 (defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments), Month 6 (defined as the average of Week 25 (Day 169) and Week 26 (Day 176) fasting assessments), and Month 12 (defined as the average of Week 51 (Day 351) and Week 52 (Day 358) fasting assessments). Abdominal pain: Weekly from Qualification to week 65 Quality of Life questionnaires: Weeks 1, 13, 26, 52, 65 Adverse events including acute pancreatitis, eruptive xanthoma: Qualification, weeks 1, 4, 8, 13, 26, 38, 52, 65 Lipemia retinalis: Qualification and Week 52 Clinical laboratory tests: Screening, weeks 1, 2, 4, 8, 12, 13, 19, 25, 26, 32, 38, 44, 51, 52, 58, 65 Echocardiography: Weeks 26 and 52 Electrocardiograms: Weeks 13, 26, 38, 52, 65 MRI: Week 52 |
misurazioni dei lipidi a digiuno: Mese 3 (definite come la media della Settimana 12 (Giorno 78) e la settimana 13 (giorno 85) valutazioni a digiuno), Mese 6 (definito come la media della Settimana 25 (Giorno 169) e la settimana 26 (Giorno 176) valutazioni a digiuno), e il mese 12 (definiti come la media della Settimana 51 (Giorno 351) e la Settimana 52 (Giorno 358) valutazioni a digiuno). Dolore addominale: settimanalmente dalla visita di Qualificazione alla settimana 65 questionari sulla qualità della vita: Settimane 1, 13, 26, 52, 65 Gli eventi avversi, tra cui pancreatite acuta, xanthoma eruttiva: alla visita di qualificazione, settimane 1, 4, 8, 13, 26, 38, 52, 65 retinalis lipemia: alla visita di qualificazione e alla settimana 52 I test clinici di laboratorio: screening, settimane |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 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 | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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.8.3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Brazil |
Canada |
France |
Germany |
Israel |
Italy |
Netherlands |
South Africa |
Spain |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |