Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying Doses and Dose Regimens of Evinacumab in Patients With Persistent Hypercholesterolemia Despite Maximally Tolerated Lipid Modifying Therapy

The primary objective of the study is to evaluate the reduction of LDL-C by evinacumab in comparison to placebo after 16 weeks in patients with primary hypercholesterolemia (HeFH, or non-HeFH with a history of clinical ASCVD) with persistent hypercholesterolemia despite receiving maximally-tolerated LMT. Persistent hypercholesterolemia is defined as LDL-C ≥70 mg/dL (1.81 mmol/L) for those patients with clinical ASCVD and LDL-C ≥100 mg/dL (2.59 mmol/L) for those patients without clinical ASCVD.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Evinacumab; Other: Background Lipid Modifying Therapy (LMT); Drug: Matching placebo

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Queensland
    • Redcliffe, Queensland, Australia, 1020
      • Redcliffe Hospital
• Austria
  • Graz, Austria, A-8036
    • Medizinische Universitaetsklinik Graz
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • University Hospital Innsbruck - Tyrolean Hospital
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5B7
      • Robarts Research Institute
    • Newmarket, Ontario, Canada, L3Y 5G8
      • SKDS Research Inc.
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Centre Etudes Cliniques Econogene-21
    • Québec, Quebec, Canada, G1V 4W2
      • Clinique des Maladies Lipidiques de Québec
• Czechia
  • Hradec Kralove, Czechia, 50008
    • University Hospital, Charles University
  • Prague, Czechia, 14021
    • Ikem Institut Klinicke A Experimentalni Mediciny
  • Prague 3
    • Praha, Prague 3, Czechia, 13000
      • CCR Prague, s.r.o
  • Praha 2
    • Karlov, Praha 2, Czechia, 121 08
      • Univerzita Karlova v Praze 1 Lekarska Fakulta
• Denmark
  • Esbjerg, Denmark, 6700
    • Sydvestjysk Sygehus
  • Herning, Denmark, 7400
    • Regionshospitalet Herning
• France
  • Dijon, France, 21079
    • Houpital Du Bocage
  • Cedex
    • Nantes, Cedex, France, 44000
      • Hopital G et R Laennec
• Israel
  • H̱olon, Israel, 58100
    • Edith Wolfson Medical Center
  • Nahariya, Israel
    • Galilee Medical Center
  • Ramat Gan, Israel, 5265601
    • Sheba MC
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center, Cardiovascular Research Center
• Italy
  • Napoli, Italy, 80131
    • Azienda Ospedaliero Universitaria Federico II di Napoli
  • Pisa, Italy, 56126
    • Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica
  • Rimini, Italy, 47923
    • Ausl Della Romagna-Ospedale Degli Infermi
  • Rome, Italy, 00185
    • Dipartimento di Medicina Traslazionale e di Precisione dell'Università degli Studi di
• Japan
  • Chuo-ku, Japan, 103-0027
    • Tokyo-Eki Center-building Clinic
  • Fujisawa-shi, Japan, 251-0041
    • Shonan Fujisawa Tokushukai Hospital
  • Hachioji, Japan, 192-0918
    • Minamino Cardiovascular Hospital
  • Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
• Jordan
  • Amman, Jordan, 11184
    • Istishari Hospital
  • Irbid, Jordan, 22110
    • King Abdullah University Hospital
  • Irbid, Jordan, 22110
    • King Abdullah University Hospital-1
  • Irbid, Jordan, 22110
    • King Abdullah University Hospital-2
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrech - Locatie AZU
  • Hoorn Noord-Hollan
    • Hoorn, Hoorn Noord-Hollan, Netherlands, 1624 NP
      • VOC Hoorn
  • Zeeland
    • Goes, Zeeland, Netherlands, 4462 RA
      • Admiraal de Ruyter Ziekenhuis
• New Zealand
  • Papamoa, New Zealand, 3118
    • Papamoa Pines Medical Centre
  • Tauranga, New Zealand, 3112
    • Clinical Horizons NZ Ltd
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Lipid and Diabetes Research Group
• Norway
  • Oslo, Norway, 0373
    • M3 Helse AS
• Poland
  • Bytom, Poland
    • Wojewodzki Szpital Specjalistyczny
  • Zabrze, Poland, 41-800
    • Slaskie Centrum Chorob Serca, III Katedra i Oddzial Kliniczny Kardiologii SUM- Oddzial Chorob Serca i Naczyn
  • Dolnoslaskie
    • Żarów, Dolnoslaskie, Poland, 58-130
      • Halina Serafin NZOZ Centrum Medyczne SERAFIN-MED
  • Podlaskie
    • Ruda Slaska, Podlaskie, Poland, 41709
      • Nzoz Przychodnia Specjalistyczna
• Russian Federation
  • Kemerovo, Russian Federation, 65000
    • Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovacsular Disease
  • Moscow, Russian Federation, 119990
    • National Research Center For Preventative Medicine of Federal Agency of High Technology Medical Aid
  • Moscow, Russian Federation, 129090
    • Federal State Budget Institution Out-patient Clinic 3
  • Novosibirsk, Russian Federation, 630089
    • NII of Therapy and Preventive Medicine
  • Rostov-on-Don, Russian Federation, 34406
    • Municipal Medical and Prophylactic Institution - City Hospital for Emergency Care No.2
  • Saint Petersburg, Russian Federation, 191186
    • Limmited Liability Company International Medical Centre SOGAZ
  • Saint Petersburg, Russian Federation, 194291
    • Federal State Institution of Healthcare Clinical Hospital #122 N.A.L.G Sokolov
  • Saint Petersburg, Russian Federation, 196084
    • LLC- Institute of Medical Research
  • Saint Petersburg, Russian Federation, 197110
    • Federal State Budgetary Institution Clinical-Diagnostic Center with Polyclinic
  • Samara, Russian Federation, 443070
    • Samara Regional Clinical Cardiologic Dispensary
  • Tomsk, Russian Federation, 34012
    • Cardiology Research Institute
• South Africa
  • Cape Town, South Africa, 7925
    • University of Cape Town
  • Parow, South Africa, 7500
    • TREAD Research CC
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2000
      • The Charlotte Maxeke Johannesburg Academic Hospital
  • West Gauteng
    • Pretoria, West Gauteng, South Africa, 182
      • Jongaie Research
  • Western Cape
    • Cape Town, Western Cape, South Africa, 713
      • Dr JM Engelbrecht Trial site
• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves (HUVN)
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • A Coruna
    • A Coruña, A Coruna, Spain, 15001
      • Hospital Universitario A Coruña
  • Aragon
    • Zaragoza, Aragon, Spain, 50009
      • Hospital Universitario Miguel Servet
• Sweden
  • Malmö, Sweden
    • Karolinska University Hospital
  • Stockholm, Sweden, 11446
    • Akardo MedSite
  • Stockholm, Sweden, SE-182 88
    • Karolinska Institutet
  • Uppsala, Sweden, 75185
    • Akademiska sjukhuset
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital-Royal Free London NHS Foundation Trust
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary - The Newcastle Upon Tyne Hospitals NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Newport Beach, California, United States, 92663-3668
      • Office of Dr. John D Homan MD
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Preventive Cardiology Inc
    • Doral, Florida, United States, 33166
      • Care Research Center Inc
    • Winter Park, Florida, United States, 32792
      • Florida Lipid Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Medical Group, Inc
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University Of Kansas Medical Center
  • Maine
    • Bangor, Maine, United States, 04401
      • EMMC Northeast Cardiology Assocites
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Heart Health Cardiology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Mt Sinai Ichan Medical Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Salisbury, North Carolina, United States, 28144
      • Rowan Diagnostic Clinic
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Capital Area Research, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center Houston
    • San Antonio, Texas, United States, 78220
      • San Antonio Premiere Internal Medicine
    • Schertz, Texas, United States, 78154
      • Clear Clinical Research, LLC
    • Tyler, Texas, United States, 75701
      • PharmaTex Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The inclusion/ exclusion criteria below, include, but are not limited to, the following:

Key Inclusion Criteria:

1. Men and women, ages 18 through 80 at the screening visit
2. Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD
3. A history of clinical ASCVD, for those patients who are non-HeFH.
4. Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at screening
5. For those patients with HeFH who are not receiving a statin at screening, documentation of inability to tolerate at least 2 statins.
6. Receiving alirocumab 150 mg SC Q2W, OR evolocumab 140 mg SC Q2W or 420 mg SC Q4W for at least 8 weeks prior to the screening visit
7. For those patients with a history of clinical ASCVD, serum LDL-C ≥ 70 mg/dL at screening (1 repeat lab is allowed)
8. For those patients without a history of clinical ASCVD, serum LDL-C ≥ 100 mg/dL at screening (1 repeat lab is allowed)
9. Provide signed informed consent

Key Exclusion Criteria:

1. Known history of homozygous FH (clinically, or by previous genotyping)
2. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
3. Newly diagnosed diabetes (within 3 months prior to screening)
4. Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before screening)

5. Laboratory findings during screening period (not including randomization labs):

   1. Triglycerides > 400 mg/dL (> 4.52 mmol/L) for patients without a known history of diabetes mellitus; OR Triglycerides > 300 mg/dL (> 3.39 mmol/L) for patients with a known history of diabetes mellitus
   2. Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody (associated with a positive HCV ribonucleic acid [RNA] polymerase chain reaction)
   3. Positive serum beta-human chorionic gonadotropin or urine pregnancy test in women of childbearing potential
   4. Estimated glomerular filtration rate < 30 mL/min/1.73 m^2
   5. TSH > 1.5 x ULN
   6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN
6. Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening visit or time of randomization
7. History of heart failure (New York Heart Association [NYHA] Class III-IV) within 12 months before screening
8. History of MI, unstable angina leading to hospitalization, CABG surgery, PCI, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, TIA, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior screening
9. History of cancer within the past 5 years (except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer)
10. Having received LDL apheresis within 2 months before screening
11. Pregnant or breast-feeding women
12. Women of childbearing potential who are unwilling to practice a highly effective birth control method
13. Men who are sexually active with women of childbearing potential (WOCBP) and are unwilling to consistently use condoms during the study drug treatment period regardless of vasectomy status.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A: dosing regimen 1; SC Evinacumab QW for 16 weeks	Drug: Evinacumab; SC or IV administration; Other Names: REGN1500; Other: Background Lipid Modifying Therapy (LMT); All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.
EXPERIMENTAL: Group A: dosing regimen 2; SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks)	Drug: Evinacumab; SC or IV administration; Other Names: REGN1500; Other: Background Lipid Modifying Therapy (LMT); All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.
EXPERIMENTAL: Group A: dosing regimen 3; SC Evinacumab QW for 16 weeks	Drug: Evinacumab; SC or IV administration; Other Names: REGN1500; Other: Background Lipid Modifying Therapy (LMT); All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.
EXPERIMENTAL: Group A: matching placebo; Placebo SC QW for 16 weeks	Other: Background Lipid Modifying Therapy (LMT); All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.; Drug: Matching placebo; SC or IV administration
EXPERIMENTAL: Group B: dosing regimen 1; Intravenous (IV) Evinacumab Q4W for 24 weeks	Drug: Evinacumab; SC or IV administration; Other Names: REGN1500; Other: Background Lipid Modifying Therapy (LMT); All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.
EXPERIMENTAL: Group B: dosing regimen 2; IV Evinacumab Q4W for 24 weeks	Drug: Evinacumab; SC or IV administration; Other Names: REGN1500; Other: Background Lipid Modifying Therapy (LMT); All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.
EXPERIMENTAL: Group B: matching placebo; Placebo IV Q4W for 24 weeks	Other: Background Lipid Modifying Therapy (LMT); All participants should be on a stable, maximally tolerated statin throughout the duration of the study. The dose of statin and of PCSK9 inhibitor, such as alirocumab or evolocumab, as well as other LMT (if applicable), should remain stable throughout the study duration, from screening through the end of study (EOS) visit.; Drug: Matching placebo; SC or IV administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand)	Baseline and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand)		Baseline and Week 16
Percent Change From Baseline in Apo B at Week 24 (ITT Estimand)		Baseline and Week 24
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand)		Baseline and Week 16
Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand)		Baseline and Week 24
Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)		Week 16
Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)		Week 16
Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand)	Percentage of Participants with Calculated LDL-C < 50 milligrams/deciliter (mg/dL) [1.30 Millimoles per liter (mmol/L)] at Week 16 (ITT Estimand)	Week 16
Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand)		Baseline and Week 24
Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand)		Baseline and Week 16
Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand)		Baseline and Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand)		Baseline and Week 16
Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand)		Baseline and Week 24
Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand)		Baseline and Week 16
Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand)		Baseline and Week 24

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Rosenson RS, Burgess LJ, Ebenbichler CF, Baum SJ, Stroes ESG, Ali S, Khilla N, Hamlin R, Pordy R, Dong Y, Son V, Gaudet D. Evinacumab in Patients with Refractory Hypercholesterolemia. N Engl J Med. 2020 Dec 10;383(24):2307-2319. doi: 10.1056/NEJMoa2031049. Epub 2020 Nov 15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 10, 2017
• Primary Completion (ACTUAL): May 22, 2020
• Study Completion (ACTUAL): December 14, 2020

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (ACTUAL): June 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: R1500-CL-1643; 2017-001508-31 (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