Efficacy and Safety of REGN727/SAR236553 Versus Placebo in Patients with Heterozygous Familial Hypercholesterolemia Not Adequately Controlled with Their Lipid-Modifying Therapy
- Conditions
- HypercholesteroleamiaMedDRA version: 17.0Level: PTClassification code 10020603Term: HypercholesterolaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2012-001222-95-GB
- Lead Sponsor
- Regeneron Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 225
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 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.;Secondary Objective: To evaluate the effect of REGN727 75 mg in comparison with placebo on LDL-C after 12 weeks of treatment<br>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)<br>To evaluate the long-term effect of REGN727 on LDL-C<br>To evaluate the safety and tolerability of REGN727<br>To evaluate the development of anti-REGN727 antibodies<br>;Primary end point(s): Percent change in LDL-C;Timepoint(s) of evaluation of this end point: From baseline to week 24
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Percent change in calculated LDL-C<br>Percent change in other lipid parameters;Timepoint(s) of evaluation of this end point: From baseline to week 12,24,52