E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heterozygous Familial Hypercholesterolemia or Non-Familial Hypercholesterolemia at High and Very High Cardiovascular Risk |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054380 |
E.1.2 | Term | Familial hypercholesterolemia |
E.1.2 | System Organ Class | 100000004850 |
|
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 | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
E.1.2 | System Organ Class | 100000004861 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068617 |
E.1.2 | Term | Coronary heart disease |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 | 10007649 |
E.1.2 | Term | Cardiovascular disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057079 |
E.1.2 | Term | Heterozygous familial hypercholesterolemia |
E.1.2 | System Organ Class | 100000004850 |
|
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 evaluate the long term safety of Praluent in patients with heterozygous familial hypercholesterolemia (heFH) or non-familial hypercholesterolemia (FH) patients at high or very high cardiovascular risk who completed the neurocognitive function study (R727-CL-1532). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• To evaluate the effect of Praluent on low-density lipoprotein cholesterol (LDL-C)
• To evaluate the effect of Praluent on other lipid parameters
• To evaluate the effect of Praluent on gonadal steroid hormones |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients having been randomized into the neurocognitive function study (R727-CL-1532) who completed treatment and the End of Study (EOS) visit with no premature or permanent discontinuation of study drug. |
|
E.4 | Principal exclusion criteria |
1. Significant protocol deviation in the parent study (neurocognitive function study, R727-CL-1532)
2. Any patient who experienced an adverse event (AE) leading to permanent discontinuation from the neurocognitive function study (R727-CL-1532).
3. Any new condition or worsening of an existing condition which would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the Open Label Extension (OLE) study
4. Known hypersensitivity to monoclonal antibody or any component of the drug product
5. Pregnant or breastfeeding women
6. Women of childbearing potential who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in the study is the incidence of adverse events (AEs) after first administration of study drug through the last dose of study drug plus 2 weeks. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weeks 0*, 8, 12, 24, 48, 72, 96, 120, 144, 168 and 192
*the End of Study (EOS) visit of the neurocognitive function study, R727-CL-1532 |
|
E.5.2 | Secondary end point(s) |
1. Calculated LDL-C values and percent changes from baseline over time
2. Values and percent changes from baseline in other lipids and other lipoproteins, including total cholesterol (Total-C), non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, and triglycerides (TGs) over time
3. Values and percent changes from baseline in gonadal hormones and gonadotropins over time |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary end points 1 and 2: Weeks 0*, 8, 24, 48, 72, 96, 120, 144, 168 and 192
Secondary end point 3: Weeks 0*, 24, 48, 72, 96, 120, 144, 168 and 192
*the End of Study (EOS) visit of the neurocognitive function study, R727-CL-1532 |
|
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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| 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 | 5 |
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 |
Bulgaria |
Chile |
Estonia |
Mexico |
Russian Federation |
South Africa |
Ukraine |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |