E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Chylomicronemia Syndrome (FCS) |
síndrome de quilomicronemia familiar (SQF) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with hypertriglyceridemia |
Pacientes con hipertrigliceridemia |
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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 | 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 |
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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 |
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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 678354 as compared to placebo on the percent change in fasting triglycerides (TG) from Baseline |
Evaluar la eficacia de ISIS 678354 en comparación con placebo en la variación porcentual de los triglicéridos (TG) en ayunas con respecto al momento basal |
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E.2.2 | Secondary objectives of the trial |
• Proportion of patients who achieve ≥ 40% reduction in fasting TG from Baseline • Percent change in fasting apoB-48 from Baseline • Proportion of patients who achieve fasting TG ≤ 750 mg/dL (8.4 mmol/L) • Adjudicated acute pancreatitis event rate in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment • Adjudicated acute pancreatitis event rate • Proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline • Proportion of patients who achieve fasting TG ≤ 500 mg/dL (5.7 mmol/L) |
• Proporción de pacientes que logran una reducción ≥ 40 % de los TG en ayunas con respecto al valor basal. • Variación porcentual de la apoB-48 en ayunas con respecto al valor basal. • Proporción de pacientes que alcanzan un valor de TG en ayunas ≤ 750 mg/dl (8,4 mmol/l). • Tasa de episodios adjudicados de pancreatitis aguda en pacientes con ≥ 2 episodios adjudicados de pancreatitis aguda en los 5 años previos a la inclusión. • Tasa de episodios adjudicados de pancreatitis aguda. • Proporción de pacientes que logran una reducción ≥ 70 % de los TG en ayunas con respecto al valor basal. • Proporción de pacientes que alcanzan un valor de TG en ayunas ≤ 500 mg/dl (5,7 mmol/l). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A diagnosis of genetically confirmed Familial Chylomicronemia Syndrome (type 1 Hyperlipoproteinemia) • Fasting TG ≥ 880 mg/dL (10 mmol/L) at Screening • History of pancreatitis. Patients without a documented history of pancreatitis are also eligible but their enrollment will be capped at 20% |
-Diagnóstico de síndrome de quilomicronemia familiar (hiperlipoproteinemia de tipo 1) -TG en ayunas ≥ 880 mg/dl (10 mmol/l) en la selección. -5. Antecedentes de pancreatitis. También podrán participar pacientes sin antecedentes registrados de pancreatitis pero su inclusión se limitará al 20 % |
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E.4 | Principal exclusion criteria |
• Acute coronary syndrome within 6 months of Screening • Major surgery within 3 months of Screening • Active pancreatitis within 4 weeks of Screening • Platelet count < 100K/mm3 at Screening or Qualification. • History of oligonucleotide associated platelet count < 75,000 mm3 • Have any other conditions, which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study |
-síndrome coronario agudo previo en los 6 meses anteriores a la selección -cirugía mayor en los 3 meses previos a la selección -Pancreatitis activa en las 4 semanas previas a la selección -Recuento de plaquetas < 100K/mm3 en la selección o calificación. -Antecedentes de recuento de plaquetas < 75.000 mm3 asociado a oligonucleótidos -Presencia de cualquier otro trastorno que, en opinión del investigador, pueda hacer que el paciente no sea apto para participar o que pueda interferir en su participación o finalización del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the percent change in fasting TG from Baseline at 6 months (average of Weeks 23, 25 and 27) compared to placebo |
El criterio de valoración principal es la variación porcentual de los TG en ayunas entre el momento basal y los 6 meses (promedio de las semanas 23, 25 y 27) en comparación con placebo. |
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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) |
Secondary endpoints include the following: • Percent change in fasting TG from Baseline at 12 months (average of Week 51 and Week 53) compared to placebo • Proportion of patients who achieve ≥ 40% reduction in fasting TG from baseline at 6 months compared to placebo • Percent change in fasting apoB-48 from Bbaseline at 6 months compared to placebo • Proportion of patients who achieve fasting TG ≤ 750 mg/dL at 6 months compared to placebo • Proportion of patients who achieve fasting TG ≤ 500 mg/dL at 6 months compared to placebo • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53) compared to placebo, in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53) compared to placebo • Proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline at 6 months compared to placebo • Proportion of patients who achieve fasting TG ≤ 500 mg/dL at 6 months compared to placebo |
Los criterios de valoración secundarios son los siguientes: • Variación porcentual de los TG en ayunas entre el momento basal y los 12 meses (promedio de las semanas 51 y 53) en comparación con placebo. • Proporción de pacientes que logran una reducción ≥ 40 % de los TG en ayunas entre el momento basal y los 6 meses en comparación con placebo. • Variación porcentual de la apoB-48 en ayunas entre el momento basal y los 6 meses en comparación con placebo. • Proporción de pacientes que alcanzan TG en ayunas ≤ 750 mg/dl a los 6 meses en comparación con placebo. • Proporción de pacientes que alcanzan TG en ayunas ≤ 500 mg/dl a los 6 meses en comparación con placebo. • Tasa de episodios adjudicados de pancreatitis aguda durante el período de tratamiento (semanas 1 a 53) en comparación con placebo, en pacientes con ≥ 2 episodios adjudicados de pancreatitis aguda en los 5 años previos a la inclusión. • Tasa de episodios validados de pancreatitis aguda durante el período de tratamiento (semanas 1 a 53) en comparación con placebo. • Proporción de pacientes que logran una reducción ≥ 70 % de los TG en ayunas entre el momento basal y los 6 meses en comparación con placebo. • Proporción de pacientes que alcanzan TG en ayunas ≤ 500 mg/dl a los 6 meses en comparación con placebo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 months and 12 months |
6 meses y 12 meses |
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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 | 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 | 14 |
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 |
Canada |
Israel |
United States |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Portugal |
Slovakia |
Spain |
Sweden |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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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LVLS |
Última Visita Último 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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |