Long Term Safety Study of PRALUENT

Long Term Safety Study of PRALUENT in Patients With Heterozygous Familial Hypercholesterolemia or With Non-Familial Hypercholesterolemia at High and Very High Cardiovascular Risk and Previously Enrolled in the Neurocognitive Function Trial

The primary objective of the study was to evaluate the long term safety of PRALUENT in participants with heterozygous familial hypercholesterolemia (heFH) or non-familial hypercholesterolemia (FH) participants at high or very high cardiovascular risk who completed the neurocognitive function study R727-CL-1532 (NCT02957682).

The secondary objectives of the study were:

• To evaluate the effect of PRALUENT on low-density lipoprotein cholesterol (LDL-C)
• To evaluate the effect of PRALUENT on other lipid parameters
• To evaluate the effect of PRALUENT on gonadal steroid hormones

Study Overview

• Status: Terminated
• Conditions: Heterozygous Familial Hypercholesterolemia; Non-familial Hypercholesterolemia
• Intervention / Treatment: Drug: Praluent

• Study Type: Interventional
• Enrollment (Actual): 1389
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • Regeneron Research Site
  • Plovdiv, Bulgaria, 4000
    • Regeneron Research Site
  • Sofia, Bulgaria, 1309
    • Regeneron Research Site
  • Sofia, Bulgaria, 1407
    • Regeneron Research Site
  • Sofia, Bulgaria, 1784
    • Regeneron Research Site #2
  • Stara Zagora, Bulgaria, 6000
    • Regeneron Research Site
  • Varna, Bulgaria, 9000
    • Regeneron Research Site
• Estonia
  • Paide, Estonia, 72713
    • Regeneron Research Site
  • Tallinn, Estonia, 10128
    • Regeneron Research Site #2
  • Tallinn, Estonia, 10617
    • Regeneron Research Site
  • Tartu, Estonia, 51014
    • Regeneron Research Site
  • Harjumaa
    • Tallinn, Harjumaa, Estonia, 10138
      • Regeneron Research Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620109
    • Regeneron Research Site
  • Ivanovo, Russian Federation, 153012
    • Regeneron Research Site
  • Kirov, Russian Federation, 610014
    • Regeneron Research Site
  • Moscow, Russian Federation, 121309
    • Regeneron Research Site
  • Moscow, Russian Federation, 121359
    • Regeneron Research Site
  • Moscow, Russian Federation, 121552
    • Regeneron Research Site
  • Novosibirsk, Russian Federation, 630008
    • Regeneron Research Site
  • Rostov-na-Donu, Russian Federation, 344068
    • Regeneron Research Site
  • Saint Petersburg, Russian Federation, 197376
    • Regeneron Research Site
  • Saint-Petersburg, Russian Federation, 193312
    • Regeneron Research Site
  • Saint-Petersburg, Russian Federation, 198205
    • Regeneron Research Site
  • Saratov, Russian Federation, 410028
    • Regeneron Research Site
  • St. Petersburg, Russian Federation, 192288
    • Regeneron Research Site #2
  • St. Petersburg, Russian Federation, 192288
    • Regeneron Research Site
  • St. Petersburg, Russian Federation, 195112
    • Regeneron Research Site
  • St. Petersburg, Russian Federation, 197376
    • Regeneron Research Site
  • St. Petersburg, Russian Federation, 197706
    • Regeneron Research Site
  • Sverdlovskaya, Russian Federation, 620109
    • Regeneron Research Site
  • Tyumen, Russian Federation, 625032
    • Regeneron Research Site
  • Yaroslavl, Russian Federation, 150030
    • Regeneron Research Site 1
  • Yaroslavl, Russian Federation, 150030
    • Regeneron Research Site 2
• South Africa
  • Bloemfontein, South Africa, 9301
    • Regeneron Research Site
  • Claremont, South Africa, 7708
    • Regeneron Research Site
  • Johannesburg, South Africa, 2013
    • Regeneron Research Site
  • Cape Town
    • Kuilsrivier, Cape Town, South Africa, 7580
      • Regeneron Research Site
    • Parow, Cape Town, South Africa, 7500
      • Regeneron Research Site
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Regeneron Research Site
  • Gauteng
    • Halfway House, Gauteng, South Africa, 1685
      • Regeneron Research Site
    • Pretoria, Gauteng, South Africa, 0002
      • Regeneron Research Site
    • Pretoria, Gauteng, South Africa, 0122
      • Regeneron Research Site
    • Pretoria, Gauteng, South Africa, 0184
      • Regeneron Research Site
    • Pretoria West, Gauteng, South Africa, 183
      • Regeneron Research Site
  • Johannesburg
    • Kempton Park, Johannesburg, South Africa, 1619
      • Regeneron Research Site
    • Soweto, Johannesburg, South Africa, 1818
      • Regeneron Research Site
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7530
      • Regeneron Research Site
    • Cape Town, Western Cape, South Africa, 7925
      • Regeneron Research Site
    • George, Western Cape, South Africa, 6529
      • Regeneron Research Site
    • Paarl, Western Cape, South Africa, 7646
      • Regeneron Research Site
    • Somerset West, Western Cape, South Africa, 7130
      • Regeneron Research Site
    • Worcester, Western Cape, South Africa, 6850
      • Regeneron Research Site
• Ukraine
  • Kharkiv, Ukraine, 61002
    • Regeneron Research Site #2
  • Kharkov, Ukraine, 61039
    • Regeneron Research Site
  • Kiev, Ukraine, 2091
    • Regeneron Research Site
  • Kyiv, Ukraine, 02002
    • Regeneron Research Site
  • Kyiv, Ukraine, 02660
    • Regeneron Research Site
  • Kyiv, Ukraine, 03037
    • Regeneron Research Site
  • Kyiv, Ukraine, 03049
    • Regeneron Research Site
  • Kyiv, Ukraine, 03115
    • Regeneron Research Site
  • Kyiv, Ukraine, 04114
    • Regeneron Research Site #2
  • Kyiv, Ukraine
    • Regeneron Research Site
  • Lviv, Ukraine, 79015
    • Regeneron Research Site
  • Uzhorod, Ukraine, 88000
    • Regeneron Research Site
  • Vinnitsa, Ukraine, 21029
    • Regeneron Research Site
  • Vinnitsya, Ukraine, 21018
    • Regeneron Research Site
  • Vinnytsya, Ukraine, 21018
    • Regeneron Research Site
• United States
  • Alabama
    • Auburn, Alabama, United States, 36830
      • Regeneron Research Site
    • Mobile, Alabama, United States, 36608
      • Regeneron Research Site
  • California
    • Beverly Hills, California, United States, 90210
      • Regeneron Research Site
    • Los Gatos, California, United States, 95032
      • Regeneron Research Site
    • North Hollywood, California, United States, 91606
      • Regeneron Research Site
    • Port Hueneme, California, United States, 93041
      • Regeneron Research Site
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Regeneron Research Site
    • Colorado Springs, Colorado, United States, 80906
      • Regeneron Research Site
  • Florida
    • Lake Worth, Florida, United States, 33461
      • Regeneron Research Site
    • Miami Springs, Florida, United States, 33166
      • Regeneron Research Site
  • Illinois
    • Champaign, Illinois, United States, 61822
      • Regeneron Research Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Regeneron Research Site
    • Indianapolis, Indiana, United States, 46237
      • Regeneron Research Site
  • Iowa
    • Ames, Iowa, United States, 50010-30144
      • Regeneron Research Site
    • Iowa City, Iowa, United States, 52242
      • Regeneron Research Site
    • Waterloo, Iowa, United States, 50702
      • Regeneron Research Site
  • Kansas
    • Newton, Kansas, United States, 67114
      • Regeneron Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Regeneron Research Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Regeneron Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Regeneron Research Site
    • Oxon Hill, Maryland, United States, 20745
      • Regeneron Research Site
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Regeneron Research Site
  • Missouri
    • Washington, Missouri, United States, 63090
      • Regeneron Research Site
  • New York
    • Buffalo, New York, United States, 14215
      • Regeneron Research Site
    • New Hyde Park, New York, United States, 11042
      • Regeneron Research Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Regeneron Research Site
    • Charlotte, North Carolina, United States, 28209
      • Regeneron Research Site
    • Charlotte, North Carolina, United States, 28277
      • Regeneron Research Site
    • Greensboro, North Carolina, United States, 27401
      • Regeneron Research Site
    • Hickory, North Carolina, United States, 28601
      • Regeneron Research Site
    • Raleigh, North Carolina, United States, 27609
      • Regeneron Research Site
    • Rocky Mount, North Carolina, United States, 27804
      • Regeneron Research Site
    • Salisbury, North Carolina, United States, 28144
      • Regeneron Research Site
    • Statesville, North Carolina, United States, 28625
      • Regeneron Research Site
    • Wilmington, North Carolina, United States, 28401
      • Regeneron Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Regeneron Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Regeneron Research Site
    • Cleveland, Ohio, United States, 44122
      • Regeneron Research Site
    • Dayton, Ohio, United States, 45414
      • Regeneron Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Regeneron Research Site
    • Summerville, South Carolina, United States, 29485
      • Regeneron Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Regeneron Research Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Regeneron Research Site
    • Knoxville, Tennessee, United States, 37760
      • Regeneron Research Site 2
    • Knoxville, Tennessee, United States, 37912
      • Regeneron Research Site 3
    • Knoxville, Tennessee, United States, 37938
      • Regeneron Research Site
    • Powell, Tennessee, United States, 37849
      • Regeneron Research Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Regeneron Research Site
    • Houston, Texas, United States, 77027
      • Regeneron Research Site
    • Schertz, Texas, United States, 78154
      • Regeneron Research Site
    • Shavano Park, Texas, United States, 78213
      • Regeneron Research Site
    • Shavano Park, Texas, United States, 78231
      • Regeneron Research Site
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Regeneron Research Site
    • Winchester, Virginia, United States, 22601
      • Regeneron Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Regeneron Research Site
    • Walla Walla, Washington, United States, 99362
      • Regeneron Research Site
  • Wisconsin
    • Manitowoc, Wisconsin, United States, 54220
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

Participants randomized into the neurocognitive function study (R727-CL-1532) who completed treatment and the end of study (EOS) visit with no premature or permanent discontinuation of study drug.

Key Exclusion Criteria:

1. Significant protocol deviation in the parent study (neurocognitive function study R727-CL-1532: NCT02957682) based on the investigator's or sponsor's judgment, such as noncompliance
2. Any participant who experienced an AE leading to permanent discontinuation from the neurocognitive function study R727-CL-1532 (NCT02957682).
3. Any new condition or worsening of an existing condition which, in the opinion of the investigator or per the PRALUENT local label, would make the participant unsuitable for enrollment or could interfere with the participant participating in or completing the open-label extension (OLE) study
4. Known hypersensitivity to monoclonal antibody or any component of the drug product
5. Pregnant or breastfeeding women

Note: Other inclusion/ exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label	Drug: Praluent; Subcutaneous (SC) administration; Other Names: SAR236553; REGN727; Alirocumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AE) After First Administration of Study Drug Through the Last Dose of Study Drug Plus 2 Weeks	An AE is any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. AEs include serious adverse events (SAEs), AEs leading to treatment discontinuation, and adverse events of special interest (AESI). AESI include local injection site reactions, general allergic events, elevated alanine aminotransferase (ALT) levels greater than or equal to (≥) 3 upper limit normal (ULN) (if baseline is less than (<) ULN)/ALT ≥2 x ULN (if baseline ≥ ULN), neurologic events, neurocognitive events (according to Customized Medical Dictionary for Regulatory Activities [MedDRA] Query [CMQ] by Sponsor grouping and CMQ by FDA grouping), cataract, new onset diabetes (NOD), hepatic disorders, and diabetes mellitus (DM)/diabetic complications.	After first administration of study drug through the last dose of study drug plus 2 weeks, up to 80 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculated Low-density Lipoprotein Cholesterol (LDL-C) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change in LDL-C From Baseline Over Time		Up to week 72
Total Cholesterol (Total-C) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change From Baseline in Total-C Over Time		Up to week 72
Lipoprotein a (Lp(a)) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change From Baseline in Lp(a) Over Time		Up to week 72
Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change From Baseline in Non-HDL-C Over Time		Up to week 72
High-density Lipoprotein Cholesterol (HDL-C) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change From Baseline in HDL-C Over Time		Up to week 72
Fasting Triglycerides (TGs) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change From Baseline in Fasting TGs Over Time		Up to week 72
Apolipoprotein B (Apo B) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change From Baseline in Apo B Over Time		Up to week 72
Apolipoprotein-A1 (Apo A1) Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Percent Change From Baseline in Apo A1 Over Time		Up to week 72
Gonadal Hormone (Follicle Stimulating Hormone [FSH] and Luteinizing Hormone [LH]) Values for Female Participants From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Gonadal Hormones (FSH and LH) for Female Participants Over Time		Up to week 72
Gonadal (FSH and LH) Hormone Values for Male Participants From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Gonadal Hormones (FSH and LH) for Male Participants Over Time		Up to week 72
Gonadotropin (Estradiol) Values for Female Participants From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Gonadotropins (Estradiol) for Female Participants Over Time		Up to week 72
Gonadotropin (Testosterone) Values for Male Participants From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Gonadotropins (Testosterone) for Male Participants Over Time		Up to week 72
Alanine Aminotransferase Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Alanine Aminotransferase Over Time		Up to week 72
Aspartate Aminotransferase Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Aspartate Aminotransferase Over Time		Up to week 72
Alkaline Phosphatase Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Alkaline Phosphatase Over Time		Up to week 72
Total Bilirubin Values From Baseline Over Time	The baseline value was defined as the last available value before the first dose of double-blind study treatment in study R727-CL-1532 (NCT02957682)	Up to week 72
Change From Baseline in Total Bilirubin Over Time		Up to week 72

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Actual): April 8, 2020
• Study Completion (Actual): April 8, 2020

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (Actual): October 3, 2018

Study Record Updates

• Last Update Posted (Actual): June 15, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: R727-CL-1609; 2018-002810-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No