Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT03175367
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 272
- Men and women, ages 18 through 80 at the screening visit
- Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD
- A history of clinical ASCVD, for those patients who are non-HeFH.
- Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at screening
- For those patients with HeFH who are not receiving a statin at screening, documentation of inability to tolerate at least 2 statins.
- 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
- For those patients with a history of clinical ASCVD, serum LDL-C ≥ 70 mg/dL at screening (1 repeat lab is allowed)
- For those patients without a history of clinical ASCVD, serum LDL-C ≥ 100 mg/dL at screening (1 repeat lab is allowed)
- Provide signed informed consent
Key
-
Known history of homozygous FH (clinically, or by previous genotyping)
-
Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
-
Newly diagnosed diabetes (within 3 months prior to screening)
-
Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before screening)
-
Laboratory findings during screening period (not including randomization labs):
- 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
- Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody (associated with a positive HCV ribonucleic acid [RNA] polymerase chain reaction)
- Positive serum beta-human chorionic gonadotropin or urine pregnancy test in women of childbearing potential
- Estimated glomerular filtration rate < 30 mL/min/1.73 m^2
- TSH > 1.5 x ULN
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN
-
Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening visit or time of randomization
-
History of heart failure (New York Heart Association [NYHA] Class III-IV) within 12 months before screening
-
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
-
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)
-
Having received LDL apheresis within 2 months before screening
-
Pregnant or breast-feeding women
-
Women of childbearing potential who are unwilling to practice a highly effective birth control method
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A: dosing regimen 1 Background Lipid Modifying Therapy (LMT) SC Evinacumab QW for 16 weeks Group A: matching placebo Matching placebo Placebo SC QW for 16 weeks Group A: dosing regimen 3 Background Lipid Modifying Therapy (LMT) SC Evinacumab QW for 16 weeks Group B: dosing regimen 1 Background Lipid Modifying Therapy (LMT) Intravenous (IV) Evinacumab Q4W for 24 weeks Group A: dosing regimen 2 Background Lipid Modifying Therapy (LMT) SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks) Group B: matching placebo Matching placebo Placebo IV Q4W for 24 weeks Group A: matching placebo Background Lipid Modifying Therapy (LMT) Placebo SC QW for 16 weeks Group B: dosing regimen 2 Evinacumab IV Evinacumab Q4W for 24 weeks Group B: dosing regimen 2 Background Lipid Modifying Therapy (LMT) IV Evinacumab Q4W for 24 weeks Group B: matching placebo Background Lipid Modifying Therapy (LMT) Placebo IV Q4W for 24 weeks Group A: dosing regimen 1 Evinacumab SC Evinacumab QW for 16 weeks Group A: dosing regimen 2 Evinacumab SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks) Group A: dosing regimen 3 Evinacumab SC Evinacumab QW for 16 weeks Group B: dosing regimen 1 Evinacumab Intravenous (IV) Evinacumab Q4W for 24 weeks
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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) Week 16 Percentage of Participants with Calculated LDL-C \< 50 milligrams/deciliter (mg/dL) \[1.30 Millimoles per liter (mmol/L)\] at Week 16 (ITT Estimand)
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
Trial Locations
- Locations (95)
Azienda Ospedaliero Universitaria Federico II di Napoli
🇮🇹Napoli, Italy
Dipartimento di Medicina Traslazionale e di Precisione dell'Università degli Studi di
🇮🇹Rome, Italy
Office of Dr. John D Homan MD
🇺🇸Newport Beach, California, United States
Clear Clinical Research, LLC
🇺🇸Schertz, Texas, United States
PharmaTex Research
🇺🇸Tyler, Texas, United States
Preventive Cardiology Inc
🇺🇸Boca Raton, Florida, United States
King Abdullah University Hospital-1
🇯🇴Irbid, Jordan
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Redcliffe Hospital
🇦🇺Redcliffe, Queensland, Australia
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Heart Health Cardiology
🇺🇸Grand Rapids, Michigan, United States
Care Research Center Inc
🇺🇸Doral, Florida, United States
Minneapolis Heart Institute Foundation
🇺🇸Minneapolis, Minnesota, United States
Medizinische Universitaetsklinik Graz
🇦🇹Graz, Austria
Clinique des maladies lipidiques de Quebec
🇨🇦Québec, Quebec, Canada
Univerzita Karlova v Praze 1 Lekarska Fakulta
🇨🇿Karlov, Praha 2, Czechia
Fondazione Toscana Gabriele Monasterio Per La Ricerca Medica E Di Sanita Pubblica
🇮🇹Pisa, Italy
Ausl Della Romagna-Ospedale Degli Infermi
🇮🇹Rimini, Italy
Tokyo-Eki Center-building Clinic
🇯🇵Chuo-ku, Japan
Minamino Cardiovascular Hospital
🇯🇵Hachioji, Japan
Saitama Medical University Hospital
🇯🇵Iruma-gun, Japan
M3 Helse AS
🇳🇴Oslo, Norway
Papamoa Pines Medical Centre
🇳🇿Papamoa, New Zealand
King Abdullah University Hospital
🇯🇴Irbid, Jordan
VOC Hoorn
🇳🇱Hoorn, Hoorn Noord-Hollan, Netherlands
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Lipid and Diabetes Research Group
🇳🇿Christchurch, Canterbury, New Zealand
Clinical Horizons NZ Ltd
🇳🇿Tauranga, New Zealand
Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovacsular Disease
🇷🇺Kemerovo, Russian Federation
University of Cape Town
🇿🇦Cape Town, South Africa
Nzoz Przychodnia Specjalistyczna
🇵🇱Ruda Slaska, Podlaskie, Poland
Hospital Universitario Virgen de las Nieves (HUVN)
🇪🇸Granada, Spain
NII of Therapy and Preventive Medicine
🇷🇺Novosibirsk, Russian Federation
Municipal Medical and Prophylactic Institution - City Hospital for Emergency Care No.2
🇷🇺Rostov-on-Don, Russian Federation
Federal State Budgetary Institution Clinical-Diagnostic Center with Polyclinic
🇷🇺Saint Petersburg, Russian Federation
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Royal Victoria Infirmary - The Newcastle Upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle Upon Tyne, United Kingdom
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario A Coruna
🇪🇸A Coruña, A Coruna, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Aragon, Spain
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Florida Lipid Institute
🇺🇸Winter Park, Florida, United States
St. Vincent Medical Group, Inc
🇺🇸Indianapolis, Indiana, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
Mt Sinai Ichan Medical Institute
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Rowan Diagnostic Clinic
🇺🇸Salisbury, North Carolina, United States
The University Of Texas Health Science Center Houston
🇺🇸Houston, Texas, United States
Wasatch Clinical Research
🇺🇸Salt Lake City, Utah, United States
Centre Etudes Cliniques Econogene-21
🇨🇦Chicoutimi, Quebec, Canada
CCR Prague, S.R.O
🇨🇿Praha, Prague 3, Czechia
University Hospital, Charles University
🇨🇿Hradec Kralove, Czechia
Ikem Institut Klinicke A Experimentalni Mediciny
🇨🇿Prague, Czechia
Sydvestjysk Sygehus
🇩🇰Esbjerg, Denmark
SKDS Research Inc.
🇨🇦Newmarket, Ontario, Canada
Regionshospitalet Herning
🇩🇰Herning, Denmark
Hopital G Et R Laennec
🇫🇷Nantes, Cedex, France
Edith Wolfson Medical Center
🇮🇱H̱olon, Israel
Houpital Du Bocage
🇫🇷Dijon, France
Galilee Medical Center
🇮🇱Nahariya, Israel
Sourasky Medical Center, Cardiovascular Research Center
🇮🇱Tel Aviv, Israel
Sheba Mc
🇮🇱Ramat Gan, Israel
Shonan Fujisawa Tokushukai Hospital
🇯🇵Fujisawa-shi, Japan
Halina Serafin NZOZ Centrum Medyczne SERAFIN-MED
🇵🇱Żarów, Dolnoslaskie, Poland
National Research Center For Preventative Medicine of Federal Agency of High Technology Medical Aid
🇷🇺Moscow, Russian Federation
Karolinska University Hospital
🇸🇪Malmö, Sweden
Karolinska Institutet
🇸🇪Stockholm, Sweden
Akademiska sjukhuset
🇸🇪Uppsala, Sweden
TREAD Research CC
🇿🇦Parow, South Africa
Jongaie Research
🇿🇦Pretoria, West Gauteng, South Africa
Hospital Universitario de Bellvitge
🇪🇸Barcelona, Spain
Akardo MedSite
🇸🇪Stockholm, Sweden
Royal Free Hospital-Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
Samara Regional Clinical Cardiologic Dispensary
🇷🇺Samara, Russian Federation
Cardiology Research Institute
🇷🇺Tomsk, Russian Federation
University Hospital Innsbruck - Tyrolean Hospital
🇦🇹Innsbruck, Tyrol, Austria
Universitair Medisch Centrum Utrech - Locatie AZU
🇳🇱Utrecht, Netherlands
Limmited Liability Company International Medical Centre SOGAZ
🇷🇺Saint Petersburg, Russian Federation
Federal State Institution of Healthcare Clinical Hospital #122 N.A.L.G Sokolov
🇷🇺Saint Petersburg, Russian Federation
King Abdullah University Hospital-2
🇯🇴Irbid, Jordan
Slaskie Centrum Chorob Serca, III Katedra i Oddzial Kliniczny Kardiologii SUM- Oddzial Chorob Serca i Naczyn
🇵🇱Zabrze, Poland
LLC- Institute of Medical Research
🇷🇺Saint Petersburg, Russian Federation
Istishari Hospital
🇯🇴Amman, Jordan
Wojewodzki Szpital Specjalistyczny
🇵🇱Bytom, Poland
EMMC Northeast Cardiology Assocites
🇺🇸Bangor, Maine, United States
Federal State Budget Institution Out-patient Clinic 3
🇷🇺Moscow, Russian Federation
Capital Area Research, LLC
🇺🇸Camp Hill, Pennsylvania, United States
San Antonio Premiere Internal Medicine
🇺🇸San Antonio, Texas, United States
Robarts Research Institute
🇨🇦London, Ontario, Canada
Admiraal de Ruyter Ziekenhuis
🇳🇱Goes, Zeeland, Netherlands
The Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦Johannesburg, Gauteng, South Africa
Dr JM Engelbrecht Trial Site
🇿🇦Cape Town, Western Cape, South Africa
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States