A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia
- Conditions
- Cardiovascular DiseasesHypertriglyceridemiaAtherosclerosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT05610280
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo in participants with hypertriglyceridemia and atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia.
- Detailed Description
This is a Phase 3, multi-center, placebo-controlled study in approximately 1475 participants with hypertriglyceridemia and atherosclerotic cardiovascular disease. The study consists of 3 periods: 1) Screening Period: Week -12 to Week -1 (up to 12 weeks); 2) Treatment Period up to Week 53; and 3) Post-Treatment Follow-up Period: Week 54 to Week 66 (13 weeks). Participants enrolled will receive olezarsen or placebo once every 4 weeks during the 53-week Treatment Period.
The Screening Period was extended with no impact to overall study timelines.
A coronary computed tomographic angiography (CTA) sub study will be performed to assess whether triglyceride lowering through inhibition of apoC-III protein synthesis may reduce coronary plaque progression.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1478
-
Participants must fall into 1 of the following groups (a or b):
a. Hypertriglyceridemia with fasting TG ≥200 mg/dL (2.26 millimoles per liter [mmol/L]) and <500 mg/dL (5.65 mmol/L) with either
-
Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or
-
At increased risk for ASCVD
b. Severe hypertriglyceridemia with fasting TG ≥500 mg/dL (5.65 mmol/L)
-
Participants should be on standard of care (SOC) lipid-lowering medications per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.
- Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening
- Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal
- Total bilirubin > 1.5 upper limit of normal unless due to Gilbert's syndrome
- Estimated GFR < 30 mL/min/1.73 m^2
NOTE: Other Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49. Olezarsen Olezarsen Participants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection up to Week 49.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo Baseline to Week 25
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein B (apoB) Compared to Placebo Baseline to Weeks 25 and 53 Percent Change From Baseline to Weeks 25 and 53 in Fasting Very Low-Density Lipoprotein-Cholesterol (VLDL)-C Compared to Placebo Baseline to Weeks 25 and 53 Percent Change From Baseline to Week 53 in Fasting TG Compared to Placebo Baseline to Week 53 Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein C-III (apoC-III) Compared to Placebo Baseline to Weeks 25 and 53 Proportion of Participants who Achieve Fasting TG <150 Milligrams per Deciliter (mg/dL) at Weeks 25 and 53 Compared to Placebo Baseline, Weeks 25 and 53 Percent Change From Baseline to Weeks 25 and 53 in Fasting non-High Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo Baseline to Weeks 25 and 53 Percent Change From Baseline to Weeks 25 and 53 in Fasting High-Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo Baseline to Weeks 25 and 53 Percent Change From Baseline to Weeks 25 and 53 in Fasting Remnant Cholesterol Compared to Placebo Baseline to Weeks 25 and 53 Percent Change From Baseline to Weeks 25 and 53 in Fasting Low-Density Lipoprotein-Cholesterol (LDL)-C Compared to Placebo Baseline to Weeks 25 and 53
Trial Locations
- Locations (166)
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
FutureMeds Sp. z o.o
🇵🇱Wrocław, Poland
Slaski Park Technologii Medycznych Kardio-Med Silesia Sp. z o. o
🇵🇱Zabrze, Poland
Cardio D&R, S.R.O. Kosice
🇸🇰Kosice, Slovakia
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Comprehensive Medical & Research Center
🇺🇸Plantation, Florida, United States
Evanston Premier Healthcare Research LLC
🇺🇸Evanston, Illinois, United States
Aa Mrc, Llc
🇺🇸Flint, Michigan, United States
Amicis Research Center
🇺🇸Valencia, California, United States
Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
🇺🇸Torrance, California, United States
Excel Clinical Medical Trials
🇺🇸Boca Raton, Florida, United States
Aultman Hospital Cardiology Clinical Trials
🇺🇸Canton, Ohio, United States
Maryland Cardiovascular Specialists
🇺🇸Baltimore, Maryland, United States
McConnell Heart Health Center
🇺🇸Columbus, Ohio, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Juno Research, LLC
🇺🇸Houston, Texas, United States
Charleston Area Medical Center (CAMC) Clinical Trials Center
🇺🇸Charleston, West Virginia, United States
Centricity Research - Oshawa Multispecialty
🇨🇦Oshawa, Ontario, Canada
Centricity Research - Toronto LMC Multispecialty
🇨🇦Toronto, Ontario, Canada
Finlay Medical Research
🇺🇸Miami, Florida, United States
Advanced Medical Research Institute (AMRI)
🇺🇸Miami, Florida, United States
Palm Research Center, Inc.
🇺🇸Las Vegas, Nevada, United States
SHATC Medica Cor EAD
🇧🇬Ruse, Bulgaria
D&A Research
🇳🇱Sneek, Netherlands
Maxima Medisch Centrum
🇳🇱Veldhoven, Netherlands
FutureMeds - Centrum Medyczne AMED Warszawa Targowek
🇵🇱Warszawa, Poland
Tennessee Center for Clinical Trials
🇺🇸Tullahoma, Tennessee, United States
Obudai Egeszsegugyi Centrum
🇭🇺Budapest, Hungary
MBAL National Cardiology Hospital
🇧🇬Sofia, Bulgaria
UMHAT Prof. Dr. Stoyan Kirkovich
🇧🇬Stara Zagora, Bulgaria
Clinexpert Kft.
🇭🇺Budapest, Hungary
Clinical Research of South Nevada
🇺🇸Las Vegas, Nevada, United States
Affinity Health Corp.
🇺🇸Nashville, Tennessee, United States
The Jackson Clinic
🇺🇸Jackson, Tennessee, United States
Albert Schweitzer Ziekenhuis
🇳🇱Zwijndrecht, Netherlands
Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD
🇧🇬Sofia, Bulgaria
Montreal Heart Institute - Institut de Cardiologie de Montreal
🇨🇦Montreal, Quebec, Canada
Het Van Weel-Bethesda Ziekenhuis
🇳🇱Dirksland, Netherlands
The Lipid Clinic (Oslo University Hospital)
🇳🇴Oslo, Norway
Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Alian, s.r.o., Kardiologicka ambulancia
🇸🇰Bardejov, Slovakia
ARC Biosystems
🇨🇦Vancouver, British Columbia, Canada
Clinique des Maladies Lipidiques de Quebec Inc.
🇨🇦Québec, Quebec, Canada
FutureMeds Warszawa Centrum
🇵🇱Warszawa, Poland
Alabama Clinical Therapeutics, LLC Alabaster
🇺🇸Birmingham, Alabama, United States
Northern California Research
🇺🇸Sacramento, California, United States
JSV Clinical Research Study, Inc
🇺🇸Tampa, Florida, United States
Louisville Metabolic and Atherosclerosis Research Center
🇺🇸Louisville, Kentucky, United States
Heart Center Research PC
🇺🇸Huntsville, Alabama, United States
Cardiovascular Research Foundation of Southern California
🇺🇸Beverly Hills, California, United States
Westside Medical Associates of Los Angeles
🇺🇸Beverly Hills, California, United States
University of California, San Diego (UCSD)
🇺🇸La Jolla, California, United States
Diabetes/Lipid Management & Research Center
🇺🇸Huntington Beach, California, United States
Metabolic Institute of America
🇺🇸Tarzana, California, United States
Clinical Trials Research
🇺🇸Lincoln, California, United States
Amicis Research
🇺🇸Northridge, California, United States
Valley Clinical Trials, Inc.
🇺🇸Northridge, California, United States
3Sync Research
🇺🇸Lake Worth, Florida, United States
Finlay Medical Research - West Palm
🇺🇸Greenacres City, Florida, United States
Global Research Associates
🇺🇸Homestead, Florida, United States
De La Cruz Research Center, LL
🇺🇸Miami, Florida, United States
Suncoast Clinical Research, Inc. - New Port Richey
🇺🇸New Port Richey, Florida, United States
Suncoast Clinical Research, Inc. - Palm Harbor
🇺🇸New Port Richey, Florida, United States
Proactive Clinical Research
🇺🇸Oakland Park, Florida, United States
Ocala Cardiovascular Research
🇺🇸Ocala, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
St. Johns Center for Clinical Research
🇺🇸Saint Augustine, Florida, United States
Centricity Research
🇺🇸Columbus, Georgia, United States
Atlanta Heart Specialists
🇺🇸Tucker, Georgia, United States
Clinical Investigation Specialists, Inc
🇺🇸Gurnee, Illinois, United States
West Broadway Clinic
🇺🇸Council Bluffs, Iowa, United States
Affinity Health
🇺🇸Park Ridge, Illinois, United States
Reid Hospital and Health Care Services
🇺🇸Richmond, Indiana, United States
Cardiovascular Research of Northwest Indiana, LLC
🇺🇸Munster, Indiana, United States
Mercy One Iowa Heart Center
🇺🇸West Des Moines, Iowa, United States
Norton Cardiovascular Associates
🇺🇸Louisville, Kentucky, United States
University of Kansas Medical Center (KUMC)
🇺🇸Kansas City, Kansas, United States
Summit Research Group, LLC
🇺🇸Stow, Ohio, United States
Moses H. Cone Memorial Hospital
🇺🇸Greensboro, North Carolina, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, North Carolina, United States
Green and Seidner Family Practice Associates
🇺🇸Lansdale, Pennsylvania, United States
Main Street Physicians Care Waterway
🇺🇸Little River, South Carolina, United States
Central Oklahoma Early Detection Center
🇺🇸Edmond, Oklahoma, United States
OnSite Clinical Solutions, LLC
🇺🇸Rock Hill, South Carolina, United States
Monument Health Clinical Research
🇺🇸Rapid City, South Dakota, United States
Health Concepts
🇺🇸Rapid City, South Dakota, United States
Texas Institute of Cardiology
🇺🇸McKinney, Texas, United States
Southern Endocrinology Associates
🇺🇸Mesquite, Texas, United States
FMC Science
🇺🇸Round Rock, Texas, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Carient Heart & Vascular
🇺🇸Manassas, Virginia, United States
MHAT Sv. Ivan Rilski - 2003 OOD
🇧🇬Dupnitsa, Bulgaria
University Multiprofile Hospital for Active Treatment Pulmed OOD
🇧🇬Plovdiv, Bulgaria
University Multiprofile Hospital for Active Treatment Alexandrovska
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment
🇧🇬Sofia, Bulgaria
Medico Dental Center ISUL Tsaritsa Yoanna EOOD
🇧🇬Sofia, Bulgaria
Specialized Hospital for Active Treatment of Cardiology
🇧🇬Varna, Bulgaria
Diagnostic Consultative Center Equita (DCC Equita)
🇧🇬Varna, Bulgaria
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Centricity Research - Vaughan Endocrinology
🇨🇦Concord, Ontario, Canada
Bluewater Clinical Research Group Inc
🇨🇦Sarnia, Ontario, Canada
Centricity Research - Etobicoke Endocrinology
🇨🇦Etobicoke, Ontario, Canada
Institute de Recherches Cliniques de Montreal
🇨🇦Montréal, Quebec, Canada
Centricity Research - Barrie Endocrinology
🇨🇦Barrie, Canada
Centricity Research - Brampton Endocrinology
🇨🇦Brampton, Canada
UNIVMED s.r.o. - Kardiologicka Ambulance
🇨🇿Brno, Czechia
Centre de Recherche Saint-Louis
🇨🇦Québec, Canada
Cevni ambulance - MATMED s.r.o.
🇨🇿Hodonin, Czechia
Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod
🇨🇿Jaroměř, Czechia
Endokrinologie Cerny Most s.r.o.
🇨🇿Prague, Czechia
Affidea Praha s.r.o.
🇨🇿Praha, Czechia
Diabetologicka a endokrinologicka ambulance Milan Kvapil s.r.o
🇨🇿Praha, Czechia
MUDr. Nina Zemkova s.r.o. Interni Ambulance
🇨🇿Uherske Hradiste, Czechia
AeskuLab k.s
🇨🇿Teplice, Czechia
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Sydvestjysk Hospital
🇩🇰Esbjerg, Denmark
Gentofte Hospital
🇩🇰Hellerup, Denmark
Godstrup Regional Hospital (Gødstrup)
🇩🇰Herning, Denmark
OUH Svendborg Hospital
🇩🇰Svendborg, Denmark
Viborg Regional Hospital
🇩🇰Viborg, Denmark
HCL Hopital Louis Pradel
🇫🇷Bron, France
CHU Dijon Bourgogne - Hopital Francois Mitterrand
🇫🇷Dijon, France
Groupement de Cooperation Sanitaire (GCS) ELSAN - Polyclinique Vauban
🇫🇷Valenciennes, France
AP-HP Hopital Pitie-Salpetriere
🇫🇷Paris, France
CRU Hungary Kft.
🇭🇺Encs, Hungary
Zuyderland Medisch Centrum
🇳🇱Heerlen, Netherlands
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
🇮🇹Bologna, Italy
GHM les Portes du Sud
🇫🇷Vénissieux, France
ASST NORD MILANO-Ospedale Edoardo Bassini
🇮🇹Cinisello Balsamo, Italy
Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna
🇮🇹Cona, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Centro Cardiologico Monzino
🇮🇹Milano, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Academic Medical Center - Department of Vascular Medicine
🇳🇱Amsterdam, Netherlands
Ziekenhuis Rijnstate
🇳🇱Arnhem, Netherlands
Deventer Ziekenhuis
🇳🇱Deventer, Netherlands
Groene Hart Ziekenhuis
🇳🇱Gouda, Netherlands
Reinier de Graaf Gasthuis
🇳🇱Delft, Netherlands
Spaarne Gasthuis
🇳🇱Haarlem, Netherlands
Bethesda Diabetes Research Center
🇳🇱Hoogeveen, Netherlands
Canisius-Wilhelmina Ziekenhuis (CWZ)
🇳🇱Nijmegen, Netherlands
Albert Schweitzer Ziekenhuis - Location Dordrecht
🇳🇱Zwijndrecht, Netherlands
SALVIA Lekston i Madej s.j.
🇵🇱Katowice, Poland
Krakowskie Centrum Medyczne Sp. z o.o.
🇵🇱Krakow, Poland
Jagiellonskie Centrum Innowacji Sp. z o.o.
🇵🇱Kraków, Poland
Praktyka Lekarska Ewa Krzyzagorska
🇵🇱Poznań, Poland
Clinical Best Solutions Sp. z.o.o Spolka Komandytowa
🇵🇱Warsaw, Poland
Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego - Panstwowy Instytut Badawczy, Klinika Kardiologii i Angiologii Interwencyjnej
🇵🇱Warsaw, Poland
ETG Zamosc - Pro Life Medica Sp. z o.o
🇵🇱Zamosc, Poland
FutureMeds
🇵🇱Łódź, Poland
Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz
🇵🇹Lisboa, Portugal
INSTYTUT CENTRUM ZDROWIA MATKI POLKI - Klinika Kardiologii i Wad Wrodzonych Doroslych
🇵🇱Łódź, Poland
Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz
🇵🇹Carnaxide, Portugal
Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
🇵🇹Vila Nova de Gaia, Portugal
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Interna SK, s.r.o., Kardiologicka a interna ambulancia
🇸🇰Svidnik, Slovakia
Hospital Germans Trias i Pujol
🇪🇸Badalona, Spain
Diab sro
🇸🇰Roznava, Slovakia
Hospital Abente y Lago
🇪🇸La Coruna, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Calle Villarroel 170
🇪🇸Barcelona, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain