E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Chylomicronemia Syndrome (FCS) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with hypertriglyceridemia |
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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 |
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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
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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
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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). |
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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 |
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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 |
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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 | 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 | 3 |
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 |
Sweden |
Netherlands |
Spain |
Germany |
Italy |
Hungary |
Norway |
Portugal |
Slovakia |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
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 |