E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe hypertryglyceridemia |
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E.1.1.1 | Medical condition in easily understood language |
Patients with increased amount of fat in blood. |
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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 olezarsen as compared to placebo on the percent change in fasting TG from Baseline |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of olezarsen as compared to placebo on:
1/ Proportion of patients who achieve fasting TG < 500 mg/dL (5.65 mmol/L) 2/ Proportion of patients who achieve fasting TG < 880 mg/dL (10 mmol/L) 3/ Proportion of patients who achieve fasting TG < 1000 mg/dL (11.29 mmol/L) 4/ Adjudicated acute pancreatitis event rate in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment 5/ Adjudicated acute pancreatitis event rate |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification - Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.
Other protocol defined criteria will apply. |
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E.4 | Principal exclusion criteria |
Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
Total bilirubin > upper limit of normal unless due to Gilbert's syndrome
Estimated GFR < 30 mL/min/1.73 m^2
Other Protocol defined exclusion criteria will apply. |
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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 Month 6 (average of Weeks 25 and 27) compared to 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) |
1. Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo 2. Proportion of Participants Who Achieve Fasting TG Less Than (<) 500 milligrams per deciliter (mg/dL) (5.7 millimoles per liter [mmol/L]) at 6 and 12 Months Compared to Placebo 3. Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 880 mg/dL 4. Proportion of Participants Who Achieve Fasting TG < 1000 mg/dL (11.29 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 1000 mg/dL 5. Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III) at 6 and 12 Months Compared to Placebo 6. Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo 7. Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo 8. Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo 9. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo, in Participants with ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment 10. Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo 11. Adjudicated acute pancreatitis event rate from Week 13 to Week 53 compared to placebo in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment. 12. Adjudicated acute pancreatitis event rate from Week 13 to Week 53 compared to placebo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2) Baseline and Month 12 3, 4) Month 6 and 12 5, 6, 7, 8) Baseline, Month 6 and 12 9, 10) Week 1 through Week 53
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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 | Yes |
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 | 4 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
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 |
New Zealand |
Australia |
Canada |
Israel |
South Africa |
Turkey |
United Kingdom |
United States |
European Union |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 11 |
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 | 5 |