A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia
A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study of Olezarsen (ISIS 678354) in Patients With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), or With Severe Hypertriglyceridemia
2 other identifiers
interventional
1,478
14 countries
168
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2022
Typical duration for phase_3
168 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 2022
CompletedFirst Posted
Study publicly available on registry
November 9, 2022
CompletedStudy Start
First participant enrolled
November 21, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 8, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 9, 2025
CompletedFebruary 10, 2026
February 1, 2026
1.7 years
November 2, 2022
February 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo
Baseline to Week 25
Secondary Outcomes (9)
Percent Change From Baseline to Week 53 in Fasting TG Compared to Placebo
Baseline to Week 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 Apolipoprotein C-III (apoC-III) 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 Weeks 25 and 53 in Fasting Remnant Cholesterol Compared to Placebo
Baseline to Weeks 25 and 53
- +4 more secondary outcomes
Study Arms (2)
Olezarsen
EXPERIMENTALParticipants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection up to Week 49.
Placebo
PLACEBO COMPARATORParticipants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (168)
Alabama Clinical Therapeutics, LLC Alabaster
Birmingham, Alabama, 35235, United States
Heart Center Research PC
Huntsville, Alabama, 35801, United States
Cardiovascular Research Foundation of Southern California
Beverly Hills, California, 90210, United States
Westside Medical Associates of Los Angeles
Beverly Hills, California, 90211, United States
Diabetes/Lipid Management & Research Center
Huntington Beach, California, 92648, United States
University of California, San Diego (UCSD)
La Jolla, California, 92037, United States
Clinical Trials Research
Lincoln, California, 95648, United States
Amicis Research
Northridge, California, 91324, United States
Valley Clinical Trials, Inc.
Northridge, California, 91325, United States
Northern California Research
Sacramento, California, 95821, United States
Amicis Research Center
Santa Clarita, California, 91344, United States
Metabolic Institute of America
Tarzana, California, 91356, United States
Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
Torrance, California, 90502, United States
Amicis Research Center
Valencia, California, 91355, United States
Excel Clinical Medical Trials
Boca Raton, Florida, 33434, United States
Finlay Medical Research - West Palm
Greenacres City, Florida, 33467, United States
Global Research Associates
Homestead, Florida, 33030, United States
3Sync Research
Lake Worth, Florida, 33460, United States
Finlay Medical Research
Miami, Florida, 33126, United States
Advanced Medical Research Institute (AMRI)
Miami, Florida, 33174, United States
De La Cruz Research Center, LL
Miami, Florida, 33184, United States
Suncoast Clinical Research, Inc. - New Port Richey
New Port Richey, Florida, 34652, United States
Suncoast Clinical Research, Inc. - Palm Harbor
New Port Richey, Florida, 34652, United States
Proactive Clinical Research
Oakland Park, Florida, 33309, United States
Ocala Cardiovascular Research
Ocala, Florida, 34471, United States
Comprehensive Medical & Research Center
Plantation, Florida, 33317, United States
Progressive Medical Research
Port Orange, Florida, 32127, United States
St. Johns Center for Clinical Research
Saint Augustine, Florida, 32086, United States
JSV Clinical Research Study, Inc
Tampa, Florida, 33634, United States
Centricity Research
Columbus, Georgia, 31904, United States
Atlanta Heart Specialists
Tucker, Georgia, 30084, United States
Evanston Premier Healthcare Research LLC
Evanston, Illinois, 60201, United States
Clinical Investigation Specialists, Inc
Gurnee, Illinois, 60031, United States
Affinity Health
Park Ridge, Illinois, 60068, United States
Cardiovascular Research of Northwest Indiana, LLC
Munster, Indiana, 46321, United States
Reid Hospital and Health Care Services
Richmond, Indiana, 47374, United States
West Broadway Clinic
Council Bluffs, Iowa, 51501, United States
Mercy One Iowa Heart Center
West Des Moines, Iowa, 50266, United States
University of Kansas Medical Center (KUMC)
Kansas City, Kansas, 66160, United States
Norton Cardiovascular Associates
Louisville, Kentucky, 40205, United States
Louisville Metabolic and Atherosclerosis Research Center
Louisville, Kentucky, 40213, United States
Maryland Cardiovascular Specialists
Baltimore, Maryland, 21229, United States
Aa Mrc, Llc
Flint, Michigan, 48504, United States
Palm Research Center, Inc.
Las Vegas, Nevada, 49148, United States
Clinical Research of South Nevada
Las Vegas, Nevada, 89104, United States
Palm Research Center, Inc.
Las Vegas, Nevada, 89148, United States
Medical University of South Carolina (MUSC)
Charleston, North Carolina, 29425, United States
Moses H. Cone Memorial Hospital
Greensboro, North Carolina, 27401, United States
Aultman Hospital Cardiology Clinical Trials
Canton, Ohio, 44710, United States
McConnell Heart Health Center
Columbus, Ohio, 43214, United States
Summit Research Group, LLC
Stow, Ohio, 44224, United States
Central Oklahoma Early Detection Center
Edmond, Oklahoma, 73034, United States
Green and Seidner Family Practice Associates
Lansdale, Pennsylvania, 19446, United States
Main Street Physicians Care Waterway
Little River, South Carolina, 29566, United States
OnSite Clinical Solutions, LLC
Rock Hill, South Carolina, 29732, United States
Monument Health Clinical Research
Rapid City, South Dakota, 57701, United States
Health Concepts
Rapid City, South Dakota, 57702, United States
The Jackson Clinic
Jackson, Tennessee, 38301, United States
Affinity Health Corp.
Nashville, Tennessee, 37203, United States
Tennessee Center for Clinical Trials
Tullahoma, Tennessee, 37388, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Juno Research, LLC
Houston, Texas, 77040, United States
Texas Institute of Cardiology
McKinney, Texas, 75071, United States
Southern Endocrinology Associates
Mesquite, Texas, 75149, United States
FMC Science
Round Rock, Texas, 78681, United States
Carient Heart & Vascular
Manassas, Virginia, 20109, United States
Manassas Clinical Research Center
Manassas, Virginia, 20110, United States
Charleston Area Medical Center (CAMC) Clinical Trials Center
Charleston, West Virginia, 25304, United States
MHAT Sv. Ivan Rilski - 2003 OOD
Dupnitsa, 2600, Bulgaria
University Multiprofile Hospital for Active Treatment Pulmed OOD
Plovdiv, 4000, Bulgaria
SHATC Medica Cor EAD
Rousse, 7013, Bulgaria
Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD
Sofia, 1000, Bulgaria
MBAL National Cardiology Hospital
Sofia, 1309, Bulgaria
University Multiprofile Hospital for Active Treatment Alexandrovska
Sofia, 1431, Bulgaria
University Multiprofile Hospital for Active Treatment
Sofia, 1431, Bulgaria
Medico Dental Center ISUL Tsaritsa Yoanna EOOD
Sofia, 1527, Bulgaria
UMHAT Prof. Dr. Stoyan Kirkovich
Stara Zagora, 6003, Bulgaria
Diagnostic Consultative Center Equita (DCC Equita)
Varna, 9000, Bulgaria
Specialized Hospital for Active Treatment of Cardiology
Varna, 9020, Bulgaria
ARC Biosystems
Vancouver, British Columbia, V6Z 2C7, Canada
Centricity Research - Vaughan Endocrinology
Concord, Ontario, L4K 4M2, Canada
Centricity Research - Etobicoke Endocrinology
Etobicoke, Ontario, M9R 4E1, Canada
Centricity Research - Oshawa Multispecialty
Oshawa, Ontario, L1J 2K9, Canada
Bluewater Clinical Research Group Inc
Sarnia, Ontario, N7t 4X3, Canada
Centricity Research - Toronto LMC Multispecialty
Toronto, Ontario, M4G 3E8, Canada
Ecogene-21
Chicoutimi, Quebec, G7H 7K9, Canada
Montreal Heart Institute - Institut de Cardiologie de Montreal
Montreal, Quebec, H1T 1C8, Canada
Institute de Recherches Cliniques de Montreal
Montreal, Quebec, H2W 1R7, Canada
Clinique des Maladies Lipidiques de Quebec Inc.
Québec, Quebec, G1V 4W2, Canada
Centricity Research - Barrie Endocrinology
Barrie, L4N 7L3, Canada
Centricity Research - Brampton Endocrinology
Brampton, L6S 6J6, Canada
Centre de Recherche Saint-Louis
Québec, G1W 4R4, Canada
UNIVMED s.r.o. - Kardiologicka Ambulance
Brno, 60300, Czechia
Cevni ambulance - MATMED s.r.o.
Hodonín, 695 01, Czechia
Edumed s.r.o., Kardiologicka, endokrinologicka, diabetologicka a interni ambulance Nachod
Jaroměř, 551 01, Czechia
Affidea Praha s.r.o.
Prague, 148 00, Czechia
Diabetologicka a endokrinologicka ambulance Milan Kvapil s.r.o
Prague, 149 00, Czechia
Endokrinologie Cerny Most s.r.o.
Prague, 19800, Czechia
AeskuLab k.s
Teplice, 415 01, Czechia
MUDr. Nina Zemkova s.r.o. Interni Ambulance
Uherské Hradiště, 686 68, Czechia
Aarhus University Hospital
Aarhus, 8000, Denmark
Sydvestjysk Hospital
Esbjerg, 6700, Denmark
Gentofte Hospital
Hellerup, 2900, Denmark
Godstrup Regional Hospital (Gødstrup)
Herning, 7400, Denmark
OUH Svendborg Hospital
Svendborg, 5700, Denmark
Viborg Regional Hospital
Viborg, 8800, Denmark
HCL Hopital Louis Pradel
Bron, 69677, France
CHU Dijon Bourgogne - Hopital Francois Mitterrand
Dijon, 21000, France
AP-HP Hopital Pitie-Salpetriere
Paris, 75013, France
Groupement de Cooperation Sanitaire (GCS) ELSAN - Polyclinique Vauban
Valenciennes, 59300, France
GHM les Portes du Sud
Vénissieux, 69200, France
Clinexpert Kft.
Budapest, 1033, Hungary
Obudai Egeszsegugyi Centrum
Budapest, H-1036, Hungary
CRU Hungary Kft.
Encs, H-3860, Hungary
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
Bologna, 40138, Italy
ASST NORD MILANO-Ospedale Edoardo Bassini
Cinisello Balsamo, 20092, Italy
Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna
Cona, 44124, Italy
Centro Cardiologico Monzino
Milan, 20138, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162, Italy
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo, 90127, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Rome, 168, Italy
Academic Medical Center - Department of Vascular Medicine
Amsterdam, 1105AZ, Netherlands
Ziekenhuis Rijnstate
Arnhem, 6815 AD, Netherlands
Reinier de Graaf Gasthuis
Delft, 2625 AD, Netherlands
Deventer Ziekenhuis
Deventer, 7416 SE, Netherlands
Het Van Weel-Bethesda Ziekenhuis
Dirksland, 3247 BW, Netherlands
Groene Hart Ziekenhuis
Gouda, 2803 HH, Netherlands
Spaarne Gasthuis
Haarlem, 2035 RC, Netherlands
Zuyderland Medisch Centrum
Heerlen, 6419 PC, Netherlands
Bethesda Diabetes Research Center
Hoogeveen, 7909 AA, Netherlands
Canisius-Wilhelmina Ziekenhuis (CWZ)
Nijmegen, 6532 SZ, Netherlands
D&A Research
Sneek, 8601 ZR, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Maxima Medisch Centrum
Veldhoven, 5504 DB, Netherlands
Albert Schweitzer Ziekenhuis - Location Dordrecht
Zwijndrecht, 3331 LZ, Netherlands
Albert Schweitzer Ziekenhuis
Zwijndrecht, 3331 LZ, Netherlands
The Lipid Clinic (Oslo University Hospital)
Oslo, 424, Norway
SALVIA Lekston i Madej s.j.
Katowice, 40-772, Poland
Jagiellonskie Centrum Innowacji Sp. z o.o.
Krakow, 30-348, Poland
Krakowskie Centrum Medyczne Sp. z o.o.
Krakow, 31-501, Poland
FutureMeds
Lodz, 91-363, Poland
INSTYTUT CENTRUM ZDROWIA MATKI POLKI - Klinika Kardiologii i Wad Wrodzonych Doroslych
Lodz, 93-338, Poland
Praktyka Lekarska Ewa Krzyzagorska
Poznan, 61-655, Poland
FutureMeds Warszawa Centrum
Warsaw, 00-215, Poland
Clinical Best Solutions Sp. z.o.o Spolka Komandytowa
Warsaw, 00-710, Poland
FutureMeds - Centrum Medyczne AMED Warszawa Targowek
Warsaw, 03-291, Poland
Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego - Panstwowy Instytut Badawczy, Klinika Kardiologii i Angiologii Interwencyjnej
Warsaw, 04-628, Poland
FutureMeds Sp. z o.o
Wroclaw, 50-088, Poland
Slaski Park Technologii Medycznych Kardio-Med Silesia Sp. z o. o
Zabrze, 48-100, Poland
ETG Zamosc - Pro Life Medica Sp. z o.o
Zamość, 22-400, Poland
Centro Hospitalar de Lisboa Ocidental. E.P.E, - Hospital Santa Cruz
Carnaxide, 2790-134, Portugal
Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Egas Moniz
Lisbon, 1349-019, Portugal
Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
Lisbon, 1649-036, Portugal
Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
Vila Nova de Gaia, 4434-502, Portugal
Alian, s.r.o., Kardiologicka ambulancia
Bardejov, 085 01, Slovakia
Cardio D&R, S.R.O. Kosice
Košice, 040 22, Slovakia
Diab sro
Rožňava, 048 01, Slovakia
Interna SK, s.r.o., Kardiologicka a interna ambulancia
Svidník, 8901, Slovakia
Hospital Abente y Lago
A Coruña, 15001, Spain
Hospital Germans Trias i Pujol
Badalona, 8916, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 8025, Spain
Calle Villarroel 170
Barcelona, 8036, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
El Palmar, 30120, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital Universitario Virgen del Rocio
Seville, 41013, Spain
Related Publications (2)
Bergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Kang YM, Weinland J, Murphy SA, Goodrich EL, Zhang S, Li D, Banach M, Stroes E, Lu MT, Tsimikas S, Giugliano RP, Sabatine MS; Essence-TIMI 73b Investigators. Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia. N Engl J Med. 2025 Oct 2;393(13):1279-1291. doi: 10.1056/NEJMoa2507227. Epub 2025 Aug 30.
PMID: 40888739DERIVEDBergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Kang YM, Murphy SA, Zhang S, Lu MT, Karwatowska-Prokopczuk E, Tsimikas S, Giugliano RP, Sabatine MS. Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk: Rationale and design of the Essence-TIMI 73b trial. Am Heart J. 2025 Aug;286:116-124. doi: 10.1016/j.ahj.2025.02.022. Epub 2025 Mar 11.
PMID: 40081744DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
November 2, 2022
First Posted
November 9, 2022
Study Start
November 21, 2022
Primary Completion
August 8, 2024
Study Completion
June 9, 2025
Last Updated
February 10, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.