A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Praluent on Neurocognitive Function in Patients With Heterozygous Familial Hypercholesterolemia or With Non-Familial Hypercholesterolemia at High and Very High Cardiovascular Risk

Regeneron Pharmaceuticals3 sites in 1 country2,176 target enrollmentNovember 2, 2016

ConditionsHypercholesterolemia

InterventionsPraluent (Alirocumab)Placebo

DrugsPraluent (Alirocumab)Placebo

Overview

Phase: Phase 4
Intervention: Praluent (Alirocumab)
Conditions: Hypercholesterolemia
Sponsor: Regeneron Pharmaceuticals
Enrollment: 2176
Locations: 3
Primary Endpoint: Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Cognitive Domain Spatial Working Memory (SWM) Strategy Z-Score at Week 96
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The main purpose of this study is to evaluate the effect on mental state (known as "neurocognitive function") with use of Praluent.

Registry

clinicaltrials.gov

Start Date

November 2, 2016

End Date

March 5, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Regeneron Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Men and women ≥ age 40 years and ≤ age 85 years
•Patients with heterozygous familial hypercholesterolemia (heFH) or with non-familial hypercholesterolemia (non-FH) patients at high or very high cardiovascular risk
•Patients with history of coronary heart disease (CHD) not having adequate control of their hypercholesterolemia with LDL-C ≥70 mg/dL, or all other patients with LDL-C ≥100 mg/dL and be on maximally-tolerated dose of statin (unless they are statin-intolerant)
•Patients must have successfully completed the Motor Screening Task
•Patients must be willing and able to comply with clinic visits and study related procedures
•Patients must provide signed informed consent

Exclusion Criteria

•Patients with known Alzheimer's disease or other dementia, schizophrenia, bipolar disorder, severe depression, cognitive impairment, or patients with a sleep disorder requiring daily pharmacological treatment
•Recent (within 3 months prior to the screening visit) myocardial infarction, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease
•Certain laboratory findings obtained during the screening visit as defined in the protocol
•Any condition or situation, including other significant mental or neurological disorders that, in the investigator's opinion, may confound the study results, or may interfere significantly with the patient's participation in the study
•Pregnant or breastfeeding women
•A positive human immunodeficiency virus (HIV) test
•NOTE: Other protocol defined Inclusion/Exclusion Criteria apply

Arms & Interventions

Group 1

Praluent Regimen - Administration through subcutaneous injection

Intervention: Praluent (Alirocumab)

Group 2

Placebo matching Praluent - Administration through subcutaneous injection

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Cognitive Domain Spatial Working Memory (SWM) Strategy Z-Score at Week 96

Time Frame: Week 96

CANTAB SWM task assessed cognitive domain of executive function. Colored boxes were shown on a screen. A token was hidden in one of the boxes (never same box twice). Instructions were to touch boxes to search for token until number of tokens found equaled number of boxes. SWM strategy index represents number of times a search began with a different box. Z-score represents standardized measure of how far an individual deviated from study cohort average at baseline. A higher Z-score reflects better performance.

Secondary Outcomes

Percent Change From Baseline in Apolipoprotein (Apo) B at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Change From Baseline in CANTAB Cognitive Domain SWM Strategy Raw Score at Week 96(Week 96)
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Percentage of Participants Who Reached Low Density Lipoprotein Cholesterol (LDL-C) Level Less Than (<) 50 mg/dL (1.29 mmol/L) at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs(Up to Week 96)
Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Percent Change From Baseline in Apolipoprotein (Apo) A-1 at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Percent Change From Baseline in Triglycerides (TG) at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)
Percentage of Participants Who Reached Low Density Lipoprotein Cholesterol (LDL-C) Level Less Than (<) 70 mg/dL (1.81 Millimoles Per Liter [mmol/L]) at Week 12, 24, 48, 72, and 96(Week 12, 24, 48, 72, and 96)