Evaluating Effect of the Study Drug Praluent (Alirocumab) on Neurocognitive Function When Compared to Placebo

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02957682
• Other study ID #: R727-CL-1532
• Secondary ID: 2016-003189-16
• Status: Completed
• Phase: Phase 4
• Start date: November 2, 2016
• Est. completion date: March 5, 2020

Study information

• Verified date: April 2021
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2176
• Est. completion date: March 5, 2020
• Est. primary completion date: March 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Key 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

Key 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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Praluent (Alirocumab)

• Placebo

Locations

Country	Name	City	State
Bulgaria	Regeneron Study Site	Pleven
Bulgaria	Regeneron Study Site	Plovdiv
Bulgaria	Regeneron Study Site	Plovdiv
Bulgaria	Regeneron Study Site	Sofia
Bulgaria	Regeneron Study Site	Sofia
Bulgaria	Regeneron Study Site	Sofia
Bulgaria	Regeneron Study Site	Stara Zagora
Bulgaria	Regeneron Study Site 1	Varna
Bulgaria	Regeneron Study Site 2	Varna
Chile	Regeneron Study Site	Osorno
Chile	Regeneron Study Site	San Miguel
Chile	Regeneron Study Site	Santiago
Chile	Regeneron Study Site	Santiago
Chile	Regeneron Study Site	Santiago
Chile	Regeneron Study Site	Santiago
Chile	Regeneron Study Site	Temuco
Chile	Regeneron Study Site	Temuco
Chile	Regeneron Study Site	Viña del Mar
Estonia	Regeneron Study Site	Paide
Estonia	Regeneron Study Site	Tallinn
Estonia	Regeneron Study Site	Tallinn
Estonia	Regeneron Study Site	Tallinn
Estonia	Regeneron Study Site	Tallinn
Estonia	Regeneron Study Site 1	Tallinn
Estonia	Regeneron Study Site 2	Tallinn
Estonia	Regeneron Study Site	Tartu
Japan	Regeneron Study Site	Bunkyo-Ku	Tokyo
Japan	Regeneron Study Site	Chuo Ku	Tokyo
Japan	Regeneron Study Site	Hachioji	Tokyo
Japan	Regeneron Study Site	Iruma-gun	Saitama
Japan	Regeneron Study Site	Itabashi-ku	Tokyo
Japan	Regeneron Study Site	Kahoku-gun	Ishikawa
Japan	Regeneron Study Site	Kawasaki	Kanagawa
Japan	Regeneron Study Site	Nakagami-gun	Okinawa
Japan	Regeneron Study Site	Nishinomiya	Hogo
Japan	Regeneron Study Site	Shinagawa-Ku	Tokyo
Japan	Regeneron Study Site	Uji-shi	Kyoto
Japan	Regeneron Study Site	Yokohama	Kanagawa
Mexico	Regeneron Study Site	Aguascalientes
Mexico	Regeneron Study Site	Cuernavaca
Mexico	Regeneron Study Site	Culiacán
Mexico	Regeneron Study Site	Distrito Federal
Mexico	Regeneron Study Site	Durango
Mexico	Regeneron Study Site	Guadalajara
Mexico	Regeneron Study Site	Guadalajara
Mexico	Regeneron Study Site	Guadalajara
Mexico	Regeneron Study Site	Merida
Mexico	Regeneron Study Site	Mexico City
Mexico	Regeneron Study Site	Mexico City
Mexico	Regeneron Study Site	Mexico City
Mexico	Regeneron Study Site	Monterrey
Mexico	Regeneron Study Site 1	Monterrey
Mexico	Regeneron Study Site 2	Monterrey
Mexico	Regeneron Study Site	Pachuca
Mexico	Regeneron Study Site	Querétaro
Mexico	Regeneron Study Site	San Juan Del Río
Mexico	Regeneron Study Site	Torreon
Russian Federation	Regeneron Study Site	Ivanovo
Russian Federation	Regeneron Study Site	Kirov
Russian Federation	Regeneron Study Site	Moscow
Russian Federation	Regeneron Study Site	Moscow
Russian Federation	Regeneron Study Site	Moscow
Russian Federation	Regeneron Study Site	Novosibirsk
Russian Federation	Regeneron Study Site	Rostov-on-Don
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	Regeneron Study Site	Saratov
Russian Federation	Regeneron Study Site	Tyumen'
Russian Federation	Regeneron Study Site	Yaroslavl
Russian Federation	Regeneron Study Site	Yaroslavl
Russian Federation	Regeneron Study Site 1	Yaroslavl
Russian Federation	Regeneron Study Site 2	Yaroslavl
South Africa	Regeneron Study Site 1	Bloemfontein
South Africa	Regeneron Study Site 2	Bloemfontein
South Africa	Regeneron Study Site	Cape Town	Western Cape
South Africa	Regeneron Study Site	Cape Town	Western Cape
South Africa	Regeneron Study Site	Claremont
South Africa	Regeneron Study Site	Halfway House	Gauteng
South Africa	Regeneron Study Site	Kempton Park	Johannesburg
South Africa	Regeneron Study Site	Kuils River	Cape Town
South Africa	Regeneron Study Site	Middelburg	Mpumalanga
South Africa	Regeneron Study Site	Paarl	Western Cape
South Africa	Regeneron Study Site	Port Elizabeth	Eastern Cape
South Africa	Regeneron Study Site	Pretoria	Gauteng
South Africa	Regeneron Study Site	Pretoria	Gauteng
South Africa	Regeneron Study Site	Pretoria West	Gauteng
South Africa	Regeneron Study Site	Somerset West	Western Cape
South Africa	Regeneron Study Site	Soweto	Johannesburg
South Africa	Regeneron Study Site	Soweto	Johannesburg
South Africa	Regeneron Study Site	Worcester	Western Cape
Ukraine	Regeneron Study Site	Kharkiv
Ukraine	Regeneron Study Site	Kharkiv
Ukraine	Regeneron Study Site	Kharkov
Ukraine	Regeneron Study Site 1	Kiev
Ukraine	Regeneron Study Site 2	Kiev
Ukraine	Regeneron Study Site	Kyiv
Ukraine	Regeneron Study Site	Kyiv
Ukraine	Regeneron Study Site	Kyiv
Ukraine	Regeneron Study Site	Kyiv
Ukraine	Regeneron Study Site 1	Kyiv
Ukraine	Regeneron Study Site 1	Kyiv
Ukraine	Regeneron Study Site 1	Kyiv
Ukraine	Regeneron Study Site 2	Kyiv
Ukraine	Regeneron Study Site 2	Kyiv
Ukraine	Regeneron Study Site 2	Kyiv
Ukraine	Regeneron Study Site	L'viv
Ukraine	Regeneron Study Site	Úzhgorod	Transcarpathian Region
Ukraine	Regeneron Study Site	Vinnitsa
Ukraine	Regeneron Study Site 1	Vinnitsa
Ukraine	Regeneron Study Site 2	Vinnitsa
United States	Regeneron Study Site	Ames	Iowa
United States	Regeneron Study Site	Auburn	Alabama
United States	Regeneron Study Site 1	Aurora	Colorado
United States	Regeneron Study Site 2	Aurora	Colorado
United States	Regeneron Study Site	Baltimore	Maryland
United States	Regeneron Study Site	Bangor	Maine
United States	Regeneron Study Site	Beverly Hills	California
United States	Regeneron Study Site	Birmingham	Alabama
United States	Regeneron Study Site	Bristol	Tennessee
United States	Regeneron Study Site	Buffalo	New York
United States	Regeneron Study Site	Burien	Washington
United States	Regeneron Study Site	Cary	North Carolina
United States	Regeneron Study Site	Champaign	Illinois
United States	Regeneron Study Site	Charleston	South Carolina
United States	Regeneron Study Site	Charlotte	North Carolina
United States	Regeneron Study Site	Charlotte	North Carolina
United States	Regeneron Study Site	Chicago	Illinois
United States	Regeneron Study Site	Chicago	Illinois
United States	Regeneron Study Site	Cincinnati	Ohio
United States	Regeneron Study Site	Cleveland	Ohio
United States	Regeneron Study Site	Colorado Springs	Colorado
United States	Regeneron Study Site	Covington	Georgia
United States	Regeneron Study Site	Dallas	Texas
United States	Regeneron Study Site	Dayton	Ohio
United States	Regeneron Study Site	Duncansville	Pennsylvania
United States	Regeneron Study Site	Evansville	Indiana
United States	Regeneron Study Site	Everett	Washington
United States	Regeneron Study Site	Falls Church	Virginia
United States	Regeneron Study Site	Greensboro	North Carolina
United States	Regeneron Study Site	Greenville	South Carolina
United States	Regeneron Study Site	Hickory	North Carolina
United States	Regeneron Study Site	High Point	North Carolina
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Houston	Texas
United States	Regeneron Study Site	Hutchinson	Kansas
United States	Regeneron Study Site	Indianapolis	Indiana
United States	Regeneron Study Site	Iowa City	Iowa
United States	Regeneron Study Site	Knoxville	Tennessee
United States	Regeneron Study Site	Knoxville	Tennessee
United States	Regeneron Study Site	Knoxville	Tennessee
United States	Regeneron Study Site	Lake Worth	Florida
United States	Regeneron Study Site	Lake Worth	Florida
United States	Regeneron Study Site	Los Gatos	California
United States	Regeneron Study Site	Louisville	Kentucky
United States	Regeneron Study Site	Manitowoc	Wisconsin
United States	Regeneron Study Site	Miami Springs	Florida
United States	Regeneron Study Site	Minneapolis	Minnesota
United States	Regeneron Study Site	Mobile	Alabama
United States	Regeneron Study Site	New Hyde Park	New York
United States	Regeneron Study Site	Newton	Kansas
United States	Regeneron Study Site	North Hollywood	California
United States	Regeneron Study Site	Olive Branch	Mississippi
United States	Regeneron Study Site	Overland Park	Kansas
United States	Regeneron Study Site	Oxon Hill	Maryland
United States	Regeneron Study Site	Port Hueneme	California
United States	Regeneron Study Site	Powell	Tennessee
United States	Regeneron Study Site	Raleigh	North Carolina
United States	Regeneron Study Site	Rapid City	South Dakota
United States	Regeneron Study Site	Rock Island	Illinois
United States	Regeneron Study Site	Rocky Mount	North Carolina
United States	Regeneron Study Site	Salisbury	North Carolina
United States	Regeneron Study Site	Schertz	Texas
United States	Regeneron Study Site	Shavano Park	Texas
United States	Regeneron Study Site	Statesville	North Carolina
United States	Regeneron Study Site	Summerville	South Carolina
United States	Regeneron Study Site	Tacoma	Washington
United States	Regeneron Study Site	Walla Walla	Washington
United States	Regeneron Study Site	Washington	Missouri
United States	Regeneron Study Site	Waterloo	Iowa
United States	Regeneron Study Site	Westminster	California
United States	Regeneron Study Site	Wilmington	North Carolina
United States	Regeneron Study Site	Winchester	Virginia
United States	Regeneron Study Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Chile,  Estonia,  Japan,  Mexico,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Cognitive Domain Spatial Working Memory (SWM) Strategy Z-Score at 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.	Week 96
Secondary	Change From Baseline in CANTAB Cognitive Domain SWM Strategy Raw Score at 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. Lower change from baseline raw scores reflect better SWM performance (i.e. less impairment).	Week 96
Secondary	Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) at Week 12, 24, 48, 72, and 96	Percent change from baseline in calculated LDL-C at Week 12, 24, 48, 72, and 96 was reported. LDL-C was measured using conventional units milligram per deciliter (mg/dL).	Week 12, 24, 48, 72, and 96
Secondary	Percent Change From Baseline in Apolipoprotein (Apo) B at Week 12, 24, 48, 72, and 96	Percent change from baseline in Apo B at Week 12, 24, 48, 72, and 96 was reported. Apo B was measured using conventional units mg/dL.	Week 12, 24, 48, 72, and 96
Secondary	Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12, 24, 48, 72, and 96	Percent change from baseline in non-HDL-C at Week 12, 24, 48, 72, and 96 was reported. Non-HDL-C was measured using conventional units mg/dL.	Week 12, 24, 48, 72, and 96
Secondary	Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12, 24, 48, 72, and 96	Percent change from baseline in calculated Total-C at Week 12, 24, 48, 72, and 96 was reported. Total-C was measured using conventional units mg/dL.	Week 12, 24, 48, 72, and 96
Secondary	Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 12, 24, 48, 72, and 96	Percent change from baseline in Lp(a) at Week 12, 24, 48, 72, and 96 was reported. Lp(a) was measured using conventional units mg/dL.	Week 12, 24, 48, 72, and 96
Secondary	Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24, 48, 72, and 96	Percent change from baseline in HDL-C at Week 12, 24, 48, 72, and 96 was reported. HDL-C was measured using conventional units mg/dL.	Week 12, 24, 48, 72, and 96
Secondary	Percent Change From Baseline in Triglycerides (TG) at Week 12, 24, 48, 72, and 96	Percent change from baseline in TG at Week 12, 24, 48, 72, and 96 was reported. TG was measured using conventional units mg/dL.	Week 12, 24, 48, 72, and 96
Secondary	Percent Change From Baseline in Apolipoprotein (Apo) A-1 at Week 12, 24, 48, 72, and 96	Percent change from baseline in Apo A-1 at Week 12, 24, 48, 72, and 96 was reported. Apo A-1 was measured using conventional units mg/dL.	Week 12, 24, 48, 72, and 96
Secondary	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	Percentage of participants who reached LDL-C level < 70 mg/dL (1.81 mmol/L) at Week 12, 24, 48, 72, and 96 were reported.	Week 12, 24, 48, 72, and 96
Secondary	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	Percentage of participants who reached LDL-C level < 50 mg/dL (1.29 mmol/L) at Week 12, 24, 48, 72, and 96 were reported.	Week 12, 24, 48, 72, and 96
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	An Adverse Event (AE) was any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. TEAE was defined as AEs that developed or worsened/became serious during on-treatment period (time from the first double-blind study treatment injection up to 70 days after the last double-blind study treatment injection). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-participant hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.	Up to Week 96