Patients with Non-familial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH) at high CV risk who are not adequately controlled with atorvastatin (20mg or 40mg) with or without other lipid-modifying therapy (LMT) (excluding EZE) MedDRA version: 14.1 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A patient must meet either 1a or 1b to be eligible for inclusion in the study: a. Patients with screening (visit 1) LDL-C ?70 mg/dL (1.81 mmol/L) who are not adequately controlled with a 20 mg or 40 mg stable daily dose of atorvastatin for at least 4 weeks before the screening visit (visit 1), with or without other LMT (excluding EZE). Patients with heFH* or non-FH must also have a history of documented CHD (defined below), or non-CHD CVD (defined below), or diabetes mellitus with target organ damage. OR b. Patients with screening (visit 1) LDL-C ?100 mg/dL (2.59 mmol/L) who are not adequately controlled with a 20 mg or 40 mg daily dose of atorvastatin for at least 4 weeks before the screening visit (visit 1), with or without other LMT (excluding EZE). Patients must also have heFH*, or have non-FH, without CHD or non-CHD CVD, but with a calculated 10-year fatal CVD risk SCORE ?5%, or with moderate CKD, or with diabetes mellitus but no target organ damage. Note: Details for the inclusion criteria are provided below. 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 350 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: LDL-C 250 mg/dL or TG >400 mg/dL Homozygous FH or patients receiving plasmapheresis CV event within 3 months prior to screening NYHA Class III or IV heart failure History of hemorrhagic stroke Uncontrolled endocrine disease known to influence serum lipids Any clinically significant abnormality that in the judgment of the investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, patients with short life expectancy, patients who cannottolerate subcutaneous injections. Use of ezetimibe or red yeast rice products within 4 weeks of screening Use of systemic corticosteroids or use of fibrates, other than fenofibrate within 6 weeks of the screening eGFR 3 x upper limit of normal (ULN) CPK >3 x ULN TSH < lower limit of normal (LLN) Hypersensitivity to monoclonal antibody therapeutics Pregnant or breast-feeding women Women of childbearing potential with no effective contraceptive method of birth control
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the reduction of low-density lipoprotein cholesterol (LDL-C) by REGN727 as add-on therapy to atorvastatin in comparison with ezetimibe (EZE) as add-on therapy to atorvastatin, in comparison with doubling the atorvastatin dose, or in comparison with a therapy switch from atorvastatin to rosuvastatin, after 24 weeks of treatment;Secondary Objective: -To evaluate the reduction of LDL-C by REGN727 75 mg as add-on therapy to atorvastatin in comparison with EZE as add-on therapy to atorvastatin, in comparison with doubling of the atorvastatin dose, or in comparison with a switch from atorvastatin to rosuvastatin after 12 weeks of treatment. -To evaluate the effect of REGN727 on other lipid parameters eg, apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (HDL-C), total-cholesterol (C), lipoprotein a (Lp[a]), HDL-C, triglycerides (TG) levels, and ApoA-1 levels. -To evaluate the safety and tolerability of REGN727. -To evaluate the development of anti-REGN727 drug antibodies (ADA).;Primary end point(s): The primary efficacy endpoint is the percent change in calculated LDL-C from baseline to week 24, which is defined as: 100x (calculated LDL-C value at week 24 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline.;Timepoint(s) of evaluation of this end point: From baseline to week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The percent change in calculated LDL-C from baseline to week 12 - The percent change in ApoB from baseline to week 24. - The percent change in non-HDL-C from baseline to week 24. - The percent change in total-C from baseline to week 24. - The percent change in ApoB from baseline to week 12. - The percent change in non-HDL-C from baseline to week 12. - The percent change in total-C from baseline to week 12. - The proportion of patients reaching LDL-C goal at week 24 - The percent change in Lp(a) from baseline to week 24. - The percent change in HDL-C from baseline to week 24. - The percent change in HDL-C from baseline to week 12. - The percent change in Lp(a) from baseline to week 12. - The percent change in fasting TG from baseline to week 24. - The percent change in fasting TG from baseline to week 12. - The percent change in ApoA-1 from baseline to week 24. - The percent change in ApoA-1 from baseline to week 12.;Timepoint(s) of evaluation of this end point: From baseline to week 12 or week 24 | — |
Countries
Australia, Brazil, Canada, France, Germany, Italy, Mexico, New Zealand, Spain, United Kingdom, United States
Contacts
Public ContactStephen Donahue, MD
Regeneron Pharmaceuticals, Inc.
Outcome results
None listed