E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Homozygous familial hypercholesterolemia |
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E.1.1.1 | Medical condition in easily understood language |
Hypercholesterolemia, also called dyslipidemia, is the presence of high levels of cholesterol in the blood |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to demonstrate the reduction of LDL-C by evinacumab 15 mg/kg IV in comparison to placebo after 24 weeks in patients with HoFH. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
• To evaluate the effect of evinacumab 15 mg/kg IV on other lipid parameters (ie, Apo B, non-HDL-C, total cholesterol [TC]) in patients with HoFH
• To evaluate the effect of evinacumab on LDL-C goal attainment
• To assess the effect of evinacumab on eligibility for apheresis (using German and US apheresis criteria)
• To evaluate the safety and tolerability of evinacumab 15 mg/kg in patients with HoFH
• To determine concentrations of evinacumab in patients with HoFH
• To evaluate the potential development of anti-evinacumab antibodies
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key inclusion criteria:
1. Male or female ≥12 years of age at the time of the screening visit
2. Diagnosis of functional HoFH
3. If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly or every other week schedule and/or stable settings for at least 8 weeks
4. Willing to consistently maintain his/her usual low fat or heart-healthy diet for the duration of the study
Note: Other protocol defined inclusion/exclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
Key exclusion criteria:
1. LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit.
2. Background medical LMT (if applicable) that has not been stable before the screening visit
3. Lipid-apheresis schedule (every 7 or 14 days)/apheresis settings (if applicable) that have not been stable for at least 8 weeks before the screening visit
4. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit
5. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
6. Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled (HbA1c >9%) diabetes
7. History of a MI, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit
8. Pregnant or breastfeeding women
9. Sexually active women of child bearing potential (WOCBP), who are unwilling to practice a highly effective birth control method prior to the initial dose, during the study, and for 24 weeks after the last dose of study drug
10. Sexually active men who are unwilling to use forms of medically acceptable birth control during the study drug treatment period and for 24 weeks after the last dose of study drug
Note: Other protocol defined inclusion/exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the percent change in calculated LDL-C from baseline to week 24. The primary endpoint is defined as: 100x (calculated LDL-C value at week 24 - calculated LDL C value at baseline)/calculated LDL-C value at baseline. |
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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) |
The key secondary endpoints are:
• The percent change in Apo B from baseline to week 24 (ITT estimand)
• The percent change in non-HDL-C from baseline to week 24 (ITT estimand)
• The percent change in TC from baseline to week 24 (ITT estimand)
• The proportion of patients with ≥30% reduction in calculated LDL-C at week 24 (ITT estimand)
• The proportion of patients with ≥50% reduction in calculated LDL-C at week 24 (ITT estimand)
• The proportion of patients with LDL-C <100 mg/dL [2.59 mmol/L] at week 24 (ITT estimand)
• The change in calculated LDL-C from baseline to week 24 (ITT estimand)
• The proportion of patients who meet EU apheresis eligibility criteria (see German Apheresis Working Group) at week 24 (ITT estimand)
• The proportion of patients who meet US apheresis eligibility criteria (see US [National Lipid Association] Lipid Apheresis Criteria) at week 24 (ITT estimand)
Refer to protocol for a full list.
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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 | Yes |
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 | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Australia |
Austria |
Canada |
Czech Republic |
France |
Germany |
Greece |
Italy |
Japan |
Netherlands |
South Africa |
Turkey |
Ukraine |
United States |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |