E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial Chylomicronemia Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Familial Chylomicronemia Syndrome - disease that prevents the body from breaking down fats consumed through the diet. |
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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 | 24.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10085051 |
E.1.2 | Term | Familial chylomicronemia syndrome |
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 |
1. To evaluate the safety of ISIS 678354 in patients with FCS previously treated with volanesorsen 2. To evaluate the tolerability of ISIS 678354 in patients with FCS previously treated with volanesorsen 3. Pharmacokinetic (PK) Objective To evaluate the PK effects of ISIS 678354 in patients with FCS previously treated with volanesorsen 4. Pharmacodynamics (PD) Objectives To evaluate the PD effects of ISIS 678354 in patients with FCS previously treated with volanesorsen |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with FCS (clinical or genetic diagnosis) currently on or previously treated with volanesorsen (ISIS 304801). Study participants in countries where Waylivra® is commercially approved and available for the patients should not be deprived of the treatment option withWaylivra®. Participation in this study for such patients will only be allowed when Waylivra® was discontinued due to adverse events (AEs)
Other protocol-defined inclusion criteria apply. |
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E.4 | Principal exclusion criteria |
Treatment with another investigational drug (non-oligonucleotide), biological agent, or device within 4 weeks of Screening, or 5 half-lives of investigational agent, whichever is longer.
Have any other conditions including significant medical history 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
Other protocol-defined exclusion criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Safety endpoints include a proportion of patients who show the following changes from Baseline to Week 53, Week 105, and Week 157: • Decrease in platelet count by > 30% • Decrease in platelet count by > 50% • Platelet count value < 50,000 mm3 • Major bleeding events • Clinically relevant non-major bleeding events • Decrease in eGFR by > 30% • Decrease in eGFR by > 50% • UPCR ≥ 1000 mg/g • UACR ≥ 500 mg/g • ALT or AST > 5 × ULN • Total bilirubin > 2.0 mg/dL • ALT or AST > 3 × ULN and total bilirubin ≥2 × ULN
2) Tolerability assessments: AEs, clinical laboratory tests, and use of concomitant medications
3) PK assessments include determination of trough (pre-dose) and post-treatment plasma ISIS 678354 concentrations
4) PD endpoints include: 1. Change and percent change from Baseline to Week 53, Week 105, and Week 157 in fasting: • TG • APOC-III, VLDL-C, chylomicron-TG total cholesterol (TC), non-HDL-C, LDL-C, apoB, apoB48, HDL-C, ApoA-1 2. Event rate of acute pancreatitis (Week 1 through Weeks 53, 105, and 157)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Baseline, Week 53, Week, 105, Week 157 2) Baseline through EoT 3) Week 1,5,13,25, 53, EoT 4) Baseline, Week, 1,5,9,13,17,21,25,29,33,37,41,45,49,53, 57,61, 105, 157, EoT |
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E.5.2 | Secondary end point(s) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |