E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Partial lipodystrophy |
lipodistrofia parziale |
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E.1.1.1 | Medical condition in easily understood language |
Patients with partial lipodystrophy |
pazienticon lipodistrofia parziale |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053857 |
E.1.2 | Term | Partial lipodystrophy |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue 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 304801 (300 mg once weekly) for reduction in severity of metabolic derangement in patients with FPL with hypertriglyceridemia and uncontrolled diabetes |
Valutare l¿efficacia di ISIS 304801 nella riduzione della gravit¿ dello squilibrio metabolico in pazienti affetti da LPF con ipertrigliceridemia e diabete non controllato. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of ISIS 304801 in patients with FPL.To further evaluate the role of serum TGs in modulating insulin resistance in FPL patients and the impact of TGs reduction on adipose tissue distribution in FPL patients |
Valutare la sicurezza e la tollerabilit¿ di ISIS 304801 nei pazienti affetti da LPF. Valutare inoltre il ruolo dei trigliceridi (TG) sierici nella modulazione dell¿nsulino-resistenza in pazienti affetti da LPF, nonch¿ l¿impatto del calo dei TG sulla distribuzione del tessuto adiposo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Clinical diagnosis of FPL plus diagnosis of type 2 diabetes mellitus and hypertriglyceridemia. 2.Diagnosis of Type 2 diabetes mellitus as defined by the ADASMCD in 2015 made at least 12 weeks prior to the screening visit 3. Hypertriglyceridemia is defined as Fasting TG = 500 mg/dL (= 5.7 mmol/L) at Screening and qualification visit. |
1 Diagnosi clinica di lipodistrofia parziale familiare più diagnosi di diabete mellito di tipo 2 e ipertrigliceridemia. 2. diagnosi di diabete mellito di tipo 2 e definito da ADASMCD 2015 effettuato almeno 12 settimane prima della visita di screenig 3 L’ipertrigliceridemia è definita come livelli di TG a digiuno = 500 mg/dl (= 5,7 mmol/l) allo screening e alla visita di idoneità. |
|
E.4 | Principal exclusion criteria |
1. A diagnosis of generalized lipodystrophy 2. A diagnosis of acquired partial lipodystrophy (APL) 3. Acute pancreatitis within 4 weeks of Screening 4. History within 6 months of Screening of acute or unstable cardiac ischemia (myocardial infarction, acute coronary syndrome, new onset angina), stroke, transient ischemic attack or unstable congestive heart failure requiring a change in medication 5. Major surgery within 3 months of Screening 6. Platelet count <lower limit of normal 7. Have any other conditions in the opinion of the investigator which could interfere with the patient participating in our completing the study |
1 Diagnosi di lipodistrofia generalizzata 2. Diagnosi di lipodistrofia parziale acquisita (acquired partial lipodystrophy, APL) 3. Pancreatite acuta nelle 4 settimane precedenti lo screening 4. Anamnesi, nei 6 mesi precedenti lo screening, di ischemia cardiaca acuta o instabile (infarto del miocardio, sindrome coronarica acuta, angina di nuova insorgenza), ictus, attacco ischemico transitorio o insufficienza cardiaca congestizia instabile che richieda una modifica dei farmaci assunti 5. Chirurgia maggiore nei 3 mesi precedenti lo screening 6 Conta piastrinica inferiore al normale limite minimo 7 presenza di altre condizioni che secondo lo Sperimentatore possono interferire con la partecipazione del paziente allo studio |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis will be the comparison of percent changes from Baseline to the primary analysis time point in fasting TG between ISIS 304801 300 mg once weekly group and placebo group in the Full Analysis Set (FAS) |
L'analisi di efficacia primaria sarà il confronto delle variazioni percentuali dal basale all'analisi primaria della valutazione a digiuno dei TG tra il gruppo trattato con ISIS 304801 300 mg e con placebo una volta alla settimana nel Full Set Analysis (FAS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments.
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il tempo di rivelazione dell'endpoint è alla fine del mese 3 in cui il valore è definito come la media delle valutazioni alla settimana 12 e la settimana 13 di digiuno. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints include: ¿ Change from baseline in HbA1c ¿ Change from Baseline in liver volume and hepatic steatosis (as assessed by MRI) ¿ Absolute change from Baseline in fasting TG ¿ Proportion of patients who achieve a = 40% reduction in fasting TG ¿ Change from Baseline in fasting plasma glucose ¿ Reduction in insulin use
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L'endpoint secondario comprende: - cambiamenti rispettoal basale di HbA1c - ambiamenti risetto al basale del volume del fegato e steatosi epatica (MRI) - variazione assoluta dal basale nei TG a digiuno - proporzione di pazienti che raggiungono pi del 40% di riduzione dei TG a digiuno - variazione rispetto al basale del livello di glucosio nel plasma a digiuno - riduzione dell'uso di insulina |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of Month 3 where the value is defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. The value at Month 6 is defined as the average of Week 25 and Week 26 and the value at Month 12 is defined as the average of Week 51 and Week 52 fasting assessments. |
Alla fine del mese 3 in cui il valore ¿ definito come la media della settimana 12 (giorno 78) e la settimana 13 (giorno 85) valutazioni a digiuno. Il valore a Mese 6 ¿ definito come la media di settimane 25 e 26 e il valore al mese 12 ¿ definito come la media della settimana 51 e la settimana 52 di valutazione a digiuno. |
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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) | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Russian Federation |
Turkey |
United States |
Belgium |
France |
Germany |
Greece |
Italy |
Netherlands |
Portugal |
Spain |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 48 |
E.8.9.2 | In all countries concerned by the trial days | 0 |