E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Chylomicronemia Syndrome (FCS) |
síndrome de hiperquilomicronemia familiar (SHQF) |
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E.1.1.1 | Medical condition in easily understood language |
Familial Chylomicronemia Syndrome (FCS) |
síndrome de hiperquilomicronemia familiar (SHQF) |
|
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 | 17.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
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.1.3 | 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) as compared to placebo on the percent change in fasting TG from baseline. |
Evaluar la eficacia de ISIS 304801 (300 mg una vez a la semana) en comparación con placebo en el cambio porcentual en los niveles de triglicéridos (TG) en ayunas respecto al periodo basal |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ISIS 304801 (300 mg once weekly) as compared to placebo on the following: ? Postprandial TG (AUC) change from baseline ? Absolute change from baseline in fasting TG ? Proportion of patients who achieve fasting TG <750 mg/dL ? Proportion of patients who achieve ?40% fasting TG reduction from baseline ? Patient reported abdominal pain o Frequency o Severity ? Composite of episodes of acute pancreatitis and patient reported abdominal pain ? Change from baseline in hepatosplenomegaly as assessed by MRI |
Evaluar la eficacia de ISIS 304801 (300 mg una vez a la semana) en comparación con placebo en: · El cambio en los niveles posprandiales de TG (AUC) respecto al periodo basal · El cambio absoluto respecto al periodo basal en los niveles de TG en ayunas · El porcentaje de pacientes que alcanza unos niveles de TG en ayunas < 750 mg/dl · El porcentaje de pacientes que consigue una reducción ? 40 % en los niveles de TG en ayunas con respecto al periodo basal · El dolor abdominal referido por los pacientes o Frecuencia o Intensidad · El criterio de valoración compuesto de acontecimientos de pancreatitis aguda y dolor abdominal referido por los pacientes · El cambio con respecto al periodo basal en la hepatoesplenomegalia evaluado mediante RM |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? History of chylomicronemia ? A diagnosis of Familial Chylomicronemia Syndrome (FCS or Type 1 Hyperlipoproteinemia) ? Fasting triglycerides ? 750 mg/dL (8.4 mmol/L) at Screening |
*Antecedentes de hiperquilomicronemia *Diagnóstico de síndrome de hiperquilomicronemia familiar (hiperlipoproteinemia de tipo I) *TG en ayunas ? 750 mg/dl (8,4 mmol/l) en el screening. |
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E.4 | Principal exclusion criteria |
? Diabetes mellitus if newly diagnosed or if HbA1c ? 9.0% ? Other types of severe hypertriglyceridemia ? Acute pancreatitis within 3 months of screening ? Acute Coronary Syndrome or major surgery within 3 months of screening ? History of heart failure ? Treatment with Glybera gene therapy within 2 years of screening ? Previous treatment with APOCIII Rx ? Have any other conditions in the opinion of the investigator which could interfere with the patient participating in or completing the study |
*Diabetes mellitus Diagnosticada por primera vez o HbA1c ? 9,0 % en el momento del screening *Otros tipos de Hipertrigliceridemia grave *Pancreatitis aguda en los 3 meses previos al screening. *síndrome coronario agudo o o cirugía mayor en los 3 meses previos al screening. *Antecedentes de insuficiencia cardíaca *Terapia génica con Glybera en los 2 años previos al screening *Tratamiento previo con APOCIII *Presencia de cualquier proceso patológico que, en opinión del investigador, haría que el paciente no fuera apto para su inclusión en el estudio, o podría interferir en la participación del paciente en el estudio o impedir que lo completase. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The % change in fasting TG from baseline as measured at the primary analysis time point. |
El criterio principal de valoración es el cambio porcentual en los niveles de TG en ayunas respecto al periodo basal, determinado en el momento del análisis principal. |
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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 (Day 78) and Week 13 (Day 85) fasting assessments. |
El momento del análisis principal es al final del tercer mes, de forma que el valor en el momento del análisis principal se define como el promedio de los valores en ayunas en las semanas 12 y 13 |
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E.5.2 | Secondary end point(s) |
? Postprandial TG (AUC) change from baseline ? Absolute change from baseline in fasting TG as measured at the primary analysis time point. ? Treatment response rate, where a patient with fasting plasma TG <750 mg/dL at the primary analysis time point is defined as a responder. If a patient terminates treatment before the primary analysis time point due to AE or lack of efficacy or other types of treatment failure, then the patient is considered as non-responder. If a patient terminates treatment before the primary analysis time point due to other reason or has missing fasting plasma TG at the primary analysis time point, then the patient will not be included in the analysis. ? Treatment response rate, where a patient who achieves fasting TG ?40% reduction from baseline at the primary analysis time point is defined as a responder. If a patient terminates treatment before the primary analysis time point due to AE or lack of efficacy or other types of treatment failure, then the patient is considered as non-responder. If a patient terminates treatment before the primary analysis time point due to other reason or has missing fasting plasma TG at the primary analysis time point, then the patient will not be included in the analysis. ? Frequency and severity of patient reported abdominal pain during the treatment period ? Composite of episodes of acute pancreatitis and patient reported abdominal pain during the treatment period ? Change from baseline in hepatosplenomegaly as assessed by MRI at Week 26 |
El cambio en los niveles posprandiales de TG (AUC) respecto al periodo basal · El cambio absoluto respecto al periodo basal en los niveles de TG en ayunas, determinado en el momento del análisis principal. · La tasa de respuesta al tratamiento, definiéndose al paciente con respuesta como el paciente con unos niveles plasmáticos de TG en ayunas < 750 mg/dl en el momento del análisis principal · La tasa de respuesta al tratamiento, definiéndose al paciente con respuesta como el paciente que consigue una reducción ? 40 % respecto al periodo basal en los niveles de TG en ayunas en el momento del análisis principal. · La frecuencia y la intensidad del dolor abdominal referido por los pacientes durante el periodo de tratamiento. · El criterio de valoración compuesto de acontecimientos de pancreatitis aguda y dolor abdominal referido por los pacientes durante el periodo de tratamiento. · El cambio con respecto al periodo basal en la hepatoesplenomegalia evaluado mediante RM |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Month 3 and Month 6 |
Mes 3 y mes 6 |
|
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | No |
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 |
Hungary |
Israel |
Italy |
Netherlands |
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
|
LVLS |
Ultima visita del ultimo paciente |
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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 | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |