Clinical trial NCT03175367: Study of Evinacumab (REGN1500) in Participants With Persistent Hypercholesterolemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-06-05
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand)
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand)
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Apo B at Week 24 (ITT Estimand)
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand)
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand)
timeFrame: Baseline and Week 24
measure: Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)
timeFrame: Week 16
measure: Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)
timeFrame: Week 16
measure: Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand)
timeFrame: Week 16
measure: Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand)
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand)
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand)
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand)
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand)
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand)
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Newport Beach
country: United States
facility: Office of Dr. John D Homan MD
state: California
city: Boca Raton
country: United States
facility: Preventive Cardiology Inc
state: Florida
city: Doral
country: United States
facility: Care Research Center Inc
state: Florida
city: Winter Park
country: United States
facility: Florida Lipid Institute
state: Florida
city: Indianapolis
country: United States
facility: St. Vincent Medical Group, Inc
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Bangor
country: United States
facility: EMMC Northeast Cardiology Assocites
state: Maine
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Heart Health Cardiology
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mt Sinai Ichan Medical Institute
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Salisbury
country: United States
facility: Rowan Diagnostic Clinic
state: North Carolina
city: Camp Hill
country: United States
facility: Capital Area Research, LLC
state: Pennsylvania
city: Houston
country: United States
facility: The University Of Texas Health Science Center Houston
state: Texas
city: San Antonio
country: United States
facility: San Antonio Premiere Internal Medicine
state: Texas
city: Schertz
country: United States
facility: Clear Clinical Research, LLC
state: Texas
city: Tyler
country: United States
facility: PharmaTex Research
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research
state: Utah
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Redcliffe
country: Australia
facility: Redcliffe Hospital
state: Queensland
city: Innsbruck
country: Austria
facility: University Hospital Innsbruck - Tyrolean Hospital
state: Tyrol
city: Graz
country: Austria
facility: Medizinische Universitaetsklinik Graz
city: London
country: Canada
facility: Robarts Research Institute
state: Ontario
city: Newmarket
country: Canada
facility: SKDS Research Inc.
state: Ontario
city: Chicoutimi
country: Canada
facility: Centre Etudes Cliniques Econogene-21
state: Quebec
city: Québec
country: Canada
facility: Clinique des maladies lipidiques de Quebec
state: Quebec
city: Praha
country: Czechia
facility: CCR Prague, S.R.O
state: Prague 3
city: Karlov
country: Czechia
facility: Univerzita Karlova v Praze 1 Lekarska Fakulta
state: Praha 2
city: Hradec Kralove
country: Czechia
facility: University Hospital, Charles University
city: Prague
country: Czechia
facility: Ikem Institut Klinicke A Experimentalni Mediciny
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus
city: Herning
country: Denmark
facility: Regionshospitalet Herning
city: Nantes
country: France
facility: Hopital G Et R Laennec
state: Cedex
city: Dijon
country: France
facility: Houpital Du Bocage
city: H̱olon
country: Israel
facility: Edith Wolfson Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Mc
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center, Cardiovascular Research Center
city: Napoli
country: Italy
facility: Azienda Ospedaliero Universitaria Federico II di Napoli
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio Per La Ricerca Medica E Di Sanita Pubblica
city: Rimini
country: Italy
facility: Ausl Della Romagna-Ospedale Degli Infermi
city: Rome
country: Italy
facility: Dipartimento di Medicina Traslazionale e di Precisione dell'Università degli Studi di
city: Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
city: Fujisawa-shi
country: Japan
facility: Shonan Fujisawa Tokushukai Hospital
city: Hachioji
country: Japan
facility: Minamino Cardiovascular Hospital
city: Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
city: Amman
country: Jordan
facility: Istishari Hospital
city: Irbid
country: Jordan
facility: King Abdullah University Hospital-1
city: Irbid
country: Jordan
facility: King Abdullah University Hospital-2
city: Irbid
country: Jordan
facility: King Abdullah University Hospital
city: Hoorn
country: Netherlands
facility: VOC Hoorn
state: Hoorn Noord-Hollan
city: Goes
country: Netherlands
facility: Admiraal de Ruyter Ziekenhuis
state: Zeeland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrech - Locatie AZU
city: Christchurch
country: New Zealand
facility: Lipid and Diabetes Research Group
state: Canterbury
city: Papamoa
country: New Zealand
facility: Papamoa Pines Medical Centre
city: Tauranga
country: New Zealand
facility: Clinical Horizons NZ Ltd
city: Oslo
country: Norway
facility: M3 Helse AS
city: Żarów
country: Poland
facility: Halina Serafin NZOZ Centrum Medyczne SERAFIN-MED
state: Dolnoslaskie
city: Ruda Slaska
country: Poland
facility: Nzoz Przychodnia Specjalistyczna
state: Podlaskie
city: Bytom
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Zabrze
country: Poland
facility: Slaskie Centrum Chorob Serca, III Katedra i Oddzial Kliniczny Kardiologii SUM- Oddzial Chorob Serca i Naczyn
city: Kemerovo
country: Russian Federation
facility: Federal State Budgetary Institution Research Institute for Complex Issues of Cardiovacsular Disease
city: Moscow
country: Russian Federation
facility: National Research Center For Preventative Medicine of Federal Agency of High Technology Medical Aid
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution Out-patient Clinic 3
city: Novosibirsk
country: Russian Federation
facility: NII of Therapy and Preventive Medicine
city: Rostov-on-Don
country: Russian Federation
facility: Municipal Medical and Prophylactic Institution - City Hospital for Emergency Care No.2
city: Saint Petersburg
country: Russian Federation
facility: Limmited Liability Company International Medical Centre SOGAZ
city: Saint Petersburg
country: Russian Federation
facility: Federal State Institution of Healthcare Clinical Hospital #122 N.A.L.G Sokolov
city: Saint Petersburg
country: Russian Federation
facility: LLC- Institute of Medical Research
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution Clinical-Diagnostic Center with Polyclinic
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Cardiologic Dispensary
city: Tomsk
country: Russian Federation
facility: Cardiology Research Institute
city: Johannesburg
country: South Africa
facility: The Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Pretoria
country: South Africa
facility: Jongaie Research
state: West Gauteng
city: Cape Town
country: South Africa
facility: Dr JM Engelbrecht Trial Site
state: Western Cape
city: Cape Town
country: South Africa
facility: University of Cape Town
city: Parow
country: South Africa
facility: TREAD Research CC
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruna
state: A Coruna
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
state: Aragon
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves (HUVN)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Malmö
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Akardo MedSite
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: London
country: United Kingdom
facility: Royal Free Hospital-Royal Free London NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary - The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.