E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
High blood cholesterol level |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020603 |
E.1.2 | Term | Hypercholesterolaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
To demonstrate the reduction of LDL-C by REGN727 as add-on therapy to stable, maximally-tolerated daily statin therapy with or without other Lipid Modifying Therapy in comparison with placebo after 24 weeks of treatment in patients with heFH. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of REGN727 75 mg in comparison with placebo on LDL-C after 12 weeks of treatment
To evaluate the effect of REGN727 on other lipid parameters (eg, ApoB, non HDL-C, total-C, Lp[a], HDL-C, TG levels, and ApoA-1 levels)
To evaluate the long-term effect of REGN727 on LDL-C
To evaluate the safety and tolerability of REGN727
To evaluate the development of anti-REGN727 antibodies
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients with heFH* who are not adequately controlled** with a maximally-tolerated daily dose*** of statin with or without other LMT, at a stable dose prior to the screening visit (week -2).
*Diagnosis of heFH must be made either by genotyping or by clinical criteria. For those patients not genotyped, the clinical diagnosis may be based on either the Simon Broome criteria for definite FH (Appendix 1) or the WHO/Dutch Lipid Network criteria with a score of >8 points (Appendix 2).
**“Not adequately controlled” is defined as LDL-C ≥70 mg/dL (1.81 mmol/L) at the screening visit (week -2) in patients with a history of documented CVD (Appendix 3), or LDL-C ≥100 mg/dL (2.59 mmol/L) at the screening visit (week -2) in patients without a history of documented CVD.
***”Maximally-tolerated dose” is defined as (any of the following are acceptable):
•Rosuvastatin 20 mg or 40 mg daily
•Atorvastatin 40 mg or 80 mg daily
•Simvastatin 80 mg daily (if already on this dose for >1 year – see exclusion criterion #7)
Note: Patients who are not able to be on any of the above statin doses should be treated with the dose of daily atorvastatin, rosuvastatin, or simvastatin which is considered appropriate for the patient, according to the investigator's judgment. Some examples of acceptable reasons for a patient taking a lower statin dose include, but are not limited to: adverse effects on higher doses, advanced age, low body mass index, regional practices, local prescribing information, concomitant medications, co-morbid conditions such as impaired glucose tolerance/impaired fasting glucose. The reason(s) will be documented in the case report form (CRF).
2.Provide signed informed consent
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E.4 | Principal exclusion criteria |
1.Patient without diagnosis of heFH made either by genotyping or by clinical criteria
2.LDL-C <70 mg/dL (<1.81 mmol/L) at the screening visit (week-2) in patients with history of documented cardiovascular disease
3.LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (week ‑2) in patients without history of documented cardiovascular disease
4.Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit (week -2) and from screening to randomization
5.Currently taking another statin than simvastatin, atorvastatin, or rosuvastatin
6.Simvastatin, atorvastatin, or rosuvastatin is not taken daily or not taken at a registered dose
7.Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for patients on simvastatin 80 mg for more than 1 year, who are eligible)
8.Use of fibrates, other than fenofibrate within 6 weeks of the screening visit (week-2) or between screening and randomization visits
9.Use of nutraceutical products or over-the-counter therapies that may affect lipids which have not been at a stable dose/amount for at least 4 weeks prior to the screening visit (week -2) or between screening and randomization visits
10.Use of red yeast rice products within 4 weeks of the screening visit (week-2), or between screening and randomization visits
11.Patient who has received plasmapheresis treatment within 2 months prior to the screening visit (week -2), or has plans to receive it during the study
12.Recent (within 3 months prior to the screening visit [week -2] or between screening and randomization visits) MI, unstable angina leading to hospitalization, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), uncontrolled cardiac arrhythmia, stroke, transient ischemic attack (TIA), carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 calculated LDL-C
Percent change in other lipid parameters |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 12,24,52 |
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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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 28 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 28 |
E.8.9.2 | In all countries concerned by the trial days | 0 |