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 |
The primary objective is to evaluate the effect of ISIS 678354 on the percent change in fasting triglycerides (TG) from Baseline |
El objetivo principal es evaluar el efecto de ISIS 678354 sobre la variación porcentual de los triglicéridos en ayunas (TG en el momento basal). |
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E.2.2 | Secondary objectives of the trial |
To evaluate effect of ISIS 678354 as compared to baseline on: • Percent change in fasting TG upon extended treatment (durability of the effect) • Proportion of patients who achieve ≥ 40% reduction in fasting TG from Baseline • Percent change in fasting apolipoprotein B (apoB) and apolipoprotein 48 (apoB48) from Baseline • Proportion of patients who achieve fasting TG ≤ 750 mg/dL • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53 in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to treatment with ISIS 678354. • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53) • Proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline • Proportion of patients who achieve fasting TG ≤ 500 mg/dL |
Evaluar el efecto de ISIS 678354 sobre: • Variación porcentual de los TG en ayunas entre el momento basal y el período de tratamiento prolongado (duración del efecto). • Proporción de pacientes que logran una reducción ≥ 40 % de los TG en ayunas con respecto al momento basal. • Variación porcentual de la apoB y la apoB48 en ayunas con respecto al momento basal. • Proporción de pacientes que logran un valor de TG en ayunas ≤ 750 mg/dl. • Tasa de episodios de pancreatitis aguda confirmados durante el período de tratamiento en pacientes con ≥ 2 episodios de pancreatitis aguda confirmados en los 5 años previos a la inclusión. • Tasa de episodios de pancreatitis aguda confirmados durante el período de tratamiento • Proporción de pacientes que logran una reducción ≥ 70 % de los TG en ayunas con respecto al momento basal. • Proporción de pacientes que logran un valor de TG en ayunas ≤ 500 mg/dl. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
2. Satisfactory completion of treatment with ISIS 678354 in the index study (last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgement 3. Willing to follow a diet comprising ≤ 20 g fat per day during the study |
2. Finalización satisfactoria del tratamiento con ISIS 678354 en el estudio de referencia (última dosis programada en la semana 49) con un perfil de seguridad aceptable, según el criterio del investigador. 3. Compromiso de seguir una dieta de ≤ 20 g de grasa por día durante la duración del estudio. |
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E.4 | Principal exclusion criteria |
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, including need for treatment with medications disallowed in the index study (ISIS 678354-CS3). |
Presencia de cualquier trastorno nuevo o empeoramiento de un trastorno existente que, en opinión del investigador, haga que el paciente no sea apto para el reclutamiento o que pueda interferir en la participación o la finalización del estudio, incluida la necesidad de tratamiento con medicamentos prohibidos en el estudio de referencia (ISIS 678354-CS3). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to evaluate safety and tolerability of treatment with ISIS 678354 |
El objetivo principal es evaluar la seguridad y la tolerabilidad del tratamiento con ISIS 678354 |
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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) |
• Percent change in fasting TG from Baseline at 6 months (average of Weeks 23, 25 and 27) • Percent change in fasting TG from Baseline at 12 months (average of Week 51 and 53) • Proportion of patients who achieve ≥ 40% reduction in fasting TG from Baseline at 6 months • Proportion of patients who achieve ≥ 40% reduction in fasting TG from Baseline at 12 months • Percent change in fasting apoB48 from Baseline at 6 months • Percent change in fasting apoB48 from Baseline at 12 months • Proportion of patients who achieve fasting TG ≤ 750 mg/dL at 6 months • Proportion of patients who achieve fasting TG ≤ 750 mg/dL at 12 months • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53), in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to treatment with ISIS 678354 • Adjudicated acute pancreatitis event rate during the Treatment Period (Week 1 through Week 53) • Proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline at 6 months • Proportion of patients who achieve ≥ 70% reduction in fasting TG from Baseline at 12 months • Proportion of patients who achieve fasting TG ≤ 500 mg/dL at 6 months • Proportion of patients who achieve fasting TG ≤ 500 mg/dL at 12 months |
• Variación porcentual de los TG en ayunas entre el momento basal y los 6 meses (media de las semanas 23, 25 y 27) • Variación porcentual de los TG en ayunas entre el momento basal y los 12 meses (media de las semanas 51 y 53) • Proporción de pacientes que logran una reducción ≥ 40 % de los TG en ayunas entre el momento basal y los 6 meses. • Proporción de pacientes que logran una reducción ≥ 40 % de los TG en ayunas entre el momento basal y los 12 meses. • Variación porcentual de la apoB48 en ayunas entre el momento basal y los 6 meses. • Variación porcentual de la apoB48 en ayunas entre el momento basal y los 12 meses. • Proporción de pacientes que logran un valor de TG en ayunas ≤ 750 mg/dl a los 6 meses. • Proporción de pacientes que logran un valor de TG en ayunas ≤ 750 mg/dl a los 12 meses. •Tasa de episodios de pancreatitis aguda confirmados durante el período de tratamiento (de la semana 1 a la semana 53) en pacientes con ≥ 2 episodios depancreatitis aguda confirmados en los 5 años previos al tratamiento con ISIS 678354. • Tasa de episodios de pancreatitis aguda confirmados durante el período de tratamiento (de la semana 1 a la semana 53). • Proporción de pacientes que logran una reducción ≥ 70 % de los TG en ayunas entre el momento basal y los 6 meses. • Proporción de pacientes que logran una reducción ≥ 70 % de los TG en ayunas entre el momento basal y los 12 meses. • Proporción de pacientes que logran un valor de TG en ayunas ≤ 500 mg/dl a los 6 meses. • Proporción de pacientes que logran un valor de TG en ayunas ≤ 500 mg/dl a los 12 meses. |
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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 | 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 | 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 | 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 | 13 |
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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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 |