A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
3 other identifiers
interventional
617
23 countries
209
Brief Summary
The purpose of the study is to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2021
Typical duration for phase_3
209 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
October 4, 2021
CompletedFirst Posted
Study publicly available on registry
October 15, 2021
CompletedStudy Start
First participant enrolled
October 25, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 22, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
July 8, 2025
CompletedFebruary 10, 2026
February 1, 2026
3 years
October 4, 2021
February 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percent Change from Baseline in Fasting TG Compared to Placebo
Baseline and Month 6
Secondary Outcomes (6)
Percent Change from Baseline in Fasting TG Compared to Placebo
Baseline and Month 12
Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III), Remnant Cholesterol and Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Compared to Placebo
Baseline, Month 6 and 12
Proportion of Patients Who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo
Month 12
Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 880 mg/dL
Month 12
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo
Week 1 through Week 53
- +1 more secondary outcomes
Study Arms (2)
Olezarsen
EXPERIMENTALOlezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.
Placebo
PLACEBO COMPARATOROlezarsen-matching placebo will be administered once every 4 weeks by SC injection from Week 1 through Week 49.
Interventions
Eligibility Criteria
You may qualify if:
- Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification
- Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) 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 \> 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 (209)
Accel Research Sites Network
Birmingham, Alabama, 35216, United States
Mayo Clinic
Scottsdale, Arizona, 85259, United States
Velocity Clinical Research
Chula Vista, California, 91911, 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
LA Universal Research Center, Inc.
Los Angeles, California, 90057, United States
America Clinical Trials
Tarzana, California, 91356, United States
Excel Medical Clinical Trials, LLC
Boca Raton, Florida, 33434, United States
Southeast Clinical Research LLC
Chiefland, Florida, 32626, United States
Westside Center for Clinical Research
Jacksonville, Florida, 32205, United States
Finlay Medical Research
Miami, Florida, 33126, United States
Innovia Research Center, INC
Miramar, Florida, 33027, United States
Ocala Cardiovascular Research
Ocala, Florida, 34471, United States
IMA Clinical Research
St. Petersburg, Florida, 33709, United States
VICIS Clinical Research
Tampa, Florida, 33614, United States
Bayside Clinical Research
Trinity, Florida, 34655, United States
IACT Health
Columbus, Georgia, 31904, United States
IMA Clinical Research Chicago
Chicago, Illinois, 60602, United States
Affinity Health
Oak Brook, Illinois, 60523, United States
West Broadway Clinic
Council Bluffs, Iowa, 51501, United States
Kansas University Medical Center
Kansas City, Kansas, 66160, United States
Clinical Trials of America, LLC
Monroe, Louisiana, 71201, United States
Continental Clinical Solutions
Towson, Maryland, 21204, United States
University of Michigan Hospital and Health Systems/ Dept. of Pharmacy-Research Pharmacy
Ann Arbor, Michigan, 48109, United States
Aa Mrc, Llc
Flint, Michigan, 48504, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
IMA Clinical Research
St Louis, Missouri, 63117, United States
Bryan Medical Center Clinical Research
Lincoln, Nebraska, 68506, United States
Palm Research Center, INC.
Las Vegas, Nevada, 89148, United States
Hudson County Clinical Trials Research Center
Union City, New Jersey, 07087, United States
Modern Medicine
Brooklyn, New York, 11235, United States
Northwell Health
Great Neck, New York, 11021, United States
Circuit Clinical (Crystal Run Healthcare)
Middletown, New York, 10941, United States
NYU Langone
New York, New York, 10016, United States
Columbia University
New York, New York, 10032, United States
Circuit Clinical
Niagara Falls, New York, 14304, United States
Modern Medical
Syosset, New York, 11791, United States
Novant Health Cancer Institute Elizabeth Investigational Drug Services
Charlotte, North Carolina, 28204, United States
Cone Medical Center
Greensboro, North Carolina, 27401, United States
Clinical Trials of America, LLC
Mount Airy, North Carolina, 27030, United States
Wake Forest University Health Sciences
Salem, North Carolina, 27157, United States
Aventiv Research
Columbus, Ohio, 43213, United States
Summit Research Group, LLC
Munroe Falls, Ohio, 44262, United States
Hightower Clinical Trial Services
Oklahoma City, Oklahoma, 73102, United States
Velocity Clinical Research
Medford, Oregon, 97504, United States
The Miriam Hospital
Providence, Rhode Island, 02906, United States
Health Concepts
Rapid City, South Dakota, 57702, United States
Chattanooga Research & Medicine, PLLC
Chattanooga, Tennessee, 37404, United States
Velocity Clinical Research
Cedar Park, Texas, 78613, United States
University of Texas Southwestern
Dallas, Texas, 75390, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Medicus Alliance Clinical Research
Sugar Land, Texas, 77478, United States
Velocity Clinical
West Jordan, Utah, 84088, United States
Manassas Clinical Research Center
Manassas, Virginia, 20110, United States
York Clinical Research LLC
Norfolk, Virginia, 23510, United States
West Virginia University Heart and Vascular Institute
Morgantown, West Virginia, 26506, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
Royal North Shoe Hospital
Saint Leonards, New South Wales, 2065, Australia
Dr. Heart Pty Ltd at Cholesterol Care Australia
Woolloongabba, Queensland, 4102, Australia
Monash Medical Centre
Clayton S., Victoria, 3168, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Royal Adelaide Hospital
Adelaide, 5000, Australia
MHAT Blagoevgrad AD
Blagoevgrad, 2700, Bulgaria
Medical Center Doctor Staykov EOOD
Burgas, 8008, Bulgaria
Medical Center Diamedical 2013 OOD
Dimitrovgrad, 6400, Bulgaria
MHAT "Dr. Tota Venkova" AD
Gabrovo, 5300, Bulgaria
Medical Center "Hera" EOOD
Montana, 3400, Bulgaria
SHAT "Special Medic" Ltd
Plovdiv, 4000, Bulgaria
Medical Center Rusemed EOOD
Rousse, 7000, Bulgaria
DCC 1 Sliven
Sliven, 8800, Bulgaria
Gabriela Zhelyazkova
Sliven, 8800, Bulgaria
Medical Center Smolyan Clinical Research OOD
Smolyan, 4700, Bulgaria
Medical Center Endomedical EOOD
Sofia, 1606, Bulgaria
Medical Centar "KALIMAT"
Sofia, 1680, Bulgaria
MC Doctor Kalchev OOD
Sofia, 1700, Bulgaria
UMHAT Sofiamed OOD
Sofia, 1797, Bulgaria
New Rehabilitation Center
Stara Zagora, 6000, Bulgaria
UMHAT Prof. Dr. Stoyan Kirkovich AD, Clinic of Cardiology
Stara Zagora, 6000, Bulgaria
Medical Centre Nevromedics EOOD
Veliko Tarnovo, 5006, Bulgaria
Arc Biosystems
Vancouver, British Columbia, V6Z 2C7, Canada
Canadian Phase Onward Inc
Toronto, Ontario, M3J 0K2, Canada
Ecogene-21
Chicoutimi, Quebec, G7H 7K9, Canada
Institut de recherches cliniques de Montréal (IRCM)
Montreal, Quebec, H2W 1R7, Canada
Clinique des Maladies Lipidiques de Quebec Inc.
Québec, Quebec, G1V 4W2, Canada
MEDICUS SERVICES s.r.o.
Brandýs nad Labem, 250 01, Czechia
EDUMED s.r.o.
Hradec Králové, 500 02, Czechia
Fakultní nemocnice Hradec Králové
Hradec Králové, 500-05, Czechia
EDUMED s.r.o.
Náchod, 547 01, Czechia
Fakultni nemocnice Ostrava
Ostrava, 70852, Czechia
Vseobecna fakultni nemocnice
Prague, 128 08, Czechia
Lekarna Poliklinika Hurka
Prague, 15800, Czechia
Interni Ambulance
Uherské Hradiště, 686 01, Czechia
Aalborg University Hospital
Aalborg, 9000, Denmark
Aarhus University Hospital
Aarhus, 8200, Denmark
Esbjerg Hospital
Esbjerg, 6700, Denmark
Bispebjerg Hospital
Frederiksberg, 2000, Denmark
Herlev Hospital
Herlev, 2730, Denmark
Godstrup Regional Hospital
Herning, 7400, Denmark
Regionshospitalet Viborg
Viborg, 8800, Denmark
Turku University Hospital
Turku, 20520, Finland
Ylitornio Health Care Center
Ylitornio, 95600, Finland
Hôpital Louis Pradel
Bron, 69677, France
CHU Dijon Bourgogne
Dijon, 21079, France
Hopital de la Conception
Marseille, 13005, France
CHU Montpellier - Hôpital Lapeyronie
Montpellier, 34295, France
Hopital Pitie Salpetriere APHP
Paris, 75013, France
CHU Nantes - Hopital Nord Laennec
Saint-Herblain, 44093, France
Stoffwechselcentrum Charite Campus Virchow
Berlin, 13353, Germany
Uniklinik Köln
Cologne, 50937, Germany
Universitaetsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 1307, Germany
Klinische Forschung Hamburg GmbH
Hamburg, 20253, Germany
Klinische Forschung Hannover-Mitte GmbH
Hanover, 30159, Germany
St. Josefskrankenhaus,
Heidelberg, 69115, Germany
Praxis Dr. med. Taggeselle
Markkleeberg, 04416, Germany
Kardiologische Praxis in Papenburg
Papenburg, 26871, Germany
Evangelisches Krankenhaus Witten
Witten, 58455, Germany
BKS Research Kft
Hatvan, Heves County, 3000, Hungary
Medifarma 98 Kft
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary
CRU Hungary Kft
Borsod, 3860, Hungary
Észak-Pesti Centrumkórház - Honvédkórház; II. Belgyógyászati Osztály
Budapest, H-1062, Hungary
Semmelweis Egyetem Kardiológiai Rehabilitacio
Budapest, H-1085, Hungary
Belinus BT
Debrecen, 4025, Hungary
Debreceni Egyetem Klinikai Kozpont Belgyogyaszat A epulet
Debrecen, 4032, Hungary
IPR Hungary Kft.
Miskolc, H-3530, Hungary
Borbanya Praxis Eü KFT
Nyíregyháza, 4405, Hungary
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
Székesfehérvár, 8000, Hungary
DRC Gyogyszervizsgalo Kozpont Kft
Veszprém, 8230, Hungary
SOROKA Medical Center
Beersheba, 8410101, Israel
Bnai Zion Medical Center
Haifa, 3339416, Israel
Lady Davis Carmel Medical Center
Haifa, 3436212, Israel
Shaare Zedek Medical Center
Jerusalem, 9103102, Israel
Hadassah Hebrew University Ein Kerm MC
Jerusalem, 91120, Israel
Rabin Medical Center
Petah Tikva, 4941492, Israel
Kaplan Medical Center
Rehovot, 7661041, Israel
Sourasky Medical Center
Tel Aviv, 6423909, Israel
Sheba Medical Center
Tel Litwinsky, 5265601, Israel
IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di SantOrsola
Bologna, 40138, Italy
Ospdale E. Bassini
Milan, 20092, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162, Italy
Azienda Ospedaliera Universitaria Federico II
Naples, 80131, Italy
A.O. Policlinico Universitario P. Giaccone
Palermo, 90127, Italy
Policlinico Umberto
Roma, 00161, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Roma, 00168, Italy
Academic Medical Center - Department of Vascular Medicine
Amsterdam, 1105 AZ, Netherlands
Rijnstate Arnhem
Arnhem, 6815 AD, Netherlands
Albert Schweitzer ziekenhuis
Dordrecht, 3318 AT, Netherlands
Ziekenhuis Gelderse Vallei
Ede, 6716 RP, Netherlands
Radboud UMC
Nijmegen, 6525 GA, Netherlands
Erasmus MC
Rotterdam, 3015 GD, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Auckland City Hospital
Grafton, Auckland, 1010, New Zealand
New Zealand Clinical Research
Christchurch, 8011, New Zealand
Wellington Regional Hospital
Newtown, 6021, New Zealand
Lipid Clinic
Oslo, 0586, Norway
Salvia
Katowice, 40-772, Poland
Praktyka Lekarska Ewa Krzyzagorska
Poznan, 61-655, Poland
ClinMedica Research Sp.z o.o.
Skierniewice, 96-100, Poland
Osrodek Badan Klinicznych Metabolica
Tarnów, 33-100, Poland
Futuremeds sp. z o.o
Wroclaw, 50-088, Poland
Instytut Centrum Zdrowia Matki Polki Klinika
Łódz, 93-338, Poland
Centro Hospitalar do Baixo Vouga Hospital Infante D. Pedro
Aveiro, 3814-501, Portugal
Centro Hospitalar e Universitário de Coimbra, EPE
Coimbra, 3004-561, Portugal
Hospital Egas Moniz - Centro Hospitalar de Lisboa Ocidental
Lisbon, 1349-019, Portugal
Centro Hospitalar Universitário de São João Consultas Externas de Endocrinologia K13
Porto, 4200-319, Portugal
Centro Hospitalar
Vila Nova de Gaia, 4434-502, Portugal
Medispektrum s.r.o., diabetologicka a metabolicka ambulancia
Bratislava, 851 01, Slovakia
Nemocnica s poliklinikou Brezno
Brezno, 97701, Slovakia
Human-Care s.r.o.
Košice, 040 01, Slovakia
Vychodoslovensky Ustav srdcovych a cievnych chorob a.s.
Košice, 040 11, Slovakia
Cardio D&R
Košice, 040 22, Slovakia
Nemocnica arm. generala L. Svobodu Svidnik,
Svidník, 089 01, Slovakia
Iatros International
Bloemfontein, Free State, 9301, South Africa
Unitas Hospital
Centurion, Gauteng, 157, South Africa
Dr Jan Engelbrecht and Ass. Inc
Cape Town, Western Cape, 7130, South Africa
TREAD Research - Department of Cardiology
Parow, Western Cape, 7500, South Africa
University of Cape town - Lipid Factory
Cape Town, 7925, South Africa
Chatsmed Garden Hospital
Chatsworth, 4092, South Africa
Hospital Abente y Lago
A Coruña, 15001, Spain
Hospital de la Santa Creu i de Sant Pau
Barcelona, 08041, Spain
Hospital Clinic Barcelona
Barcelona, 8063, Spain
Institut d'Investigació i Innovació Parc Taulí (I3PT) Departament Medicina Universitat
Barcelona, 8208, Spain
Hospital Universitari de Bellvitge
Barcelona, 8907, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Clinica Universidad de Navarra
Madrid, 28027, Spain
Hospital Universitario
Madrid, 28041, Spain
Hospital Virgen del Rocio Edificio Centro de Diagnostico y Tratamiento (CDT)
Seville, 41013, Spain
Hospital Universitari Sant Joan de Reus.
Tarragona, 43204, Spain
Sahlgrenska, University Hospital
Gothenburg, Västra Götaland County, 413 45, Sweden
Karolinska University Hospital Huddinge
Stockholm, 14186, Sweden
Hacettepe University Medical Faculty
Ankara, 06230, Turkey (Türkiye)
Ege University School of Medicine, Department of Cardiology
Izmir, 35100, Turkey (Türkiye)
Kocaeli University Faculty of Medicine
Kocaeli, 41380, Turkey (Türkiye)
Necmettin Erbakan University Meram Medical Faculty
Konya, 42280, Turkey (Türkiye)
Oak Tree Surgery and Pensilva Health Centre
Liskeard, Cornwall, PL14 3XA, United Kingdom
Newquay Health Centre
Newquay, Cornwall, TR7 1RU, United Kingdom
Upton Surgery
Poole, Dorset, BH16 5PW, United Kingdom
Panthera Biopartners
Rochdale, England, OL11 4AU, United Kingdom
Panthera Biopartners
Sheffield, England, S2 5FX, United Kingdom
Huddersfield Royal Infirmary
Lindley, Huddersfield, HD3 3EA, United Kingdom
Lakeside Healthcare at Corby
Corby, Northamptonshire, NN172UR, United Kingdom
Sandwell General Hospital
Lyne, West Bromwich, B71 4HJ, United Kingdom
Waterloo Medical Centre
Blackpool, FY4 3AD, United Kingdom
Mounts Bay Medical Hub
Cornwell, TR27 5DT, United Kingdom
Panthera
Glasgow, G51 4TY, United Kingdom
Hull Royal Infirmary
Hull, HU3 2JZ, United Kingdom
Panthera
London, EN3 4GS, United Kingdom
Manchester University NHS Foundation Trust (MFT)
Manchester, M13 9WL, United Kingdom
Panthera
Preston, PR2 9QB, United Kingdom
Primary Care Sheffield
Sheffield, S94EU, United Kingdom
Related Publications (2)
Marston NA, Bergmark BA, Alexander VJ, Prohaska TA, Kang YM, Moura FA, Zimerman A, Waldman E, Weinland J, Murphy SA, Goodrich EL, Zhang S, Xia S, Li D, Goldberg AC, Goudev A, Badimon L, Kiss RG, Vrablik M, Gaudet D, Moulin P, Stroes ESG, Banach M, Cohen H, Blom D, Charng MJ, Nordestgaard BG, Nicholls SJ, Tsimikas S, Giugliano RP, Sabatine MS; CORE-TIMI 72a and CORE2-TIMI 72b Investigators. Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk. N Engl J Med. 2026 Jan 29;394(5):429-441. doi: 10.1056/NEJMoa2512761. Epub 2025 Nov 8.
PMID: 41211918DERIVEDMarston NA, Bergmark BA, Alexander VJ, Karwatowska-Prokopczuk E, Kang YM, Moura FA, Prohaska TA, Zimerman A, Zhang S, Murphy SA, Tsimikas S, Giugliano RP, Sabatine MS. Design and rationale of the CORE-TIMI 72a and CORE2-TIMI 72b trials of olezarsen in patients with severe hypertriglyceridemia. Am Heart J. 2025 Aug;286:125-135. doi: 10.1016/j.ahj.2025.03.003. Epub 2025 Mar 9.
PMID: 40064331DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
October 4, 2021
First Posted
October 15, 2021
Study Start
October 25, 2021
Primary Completion
October 22, 2024
Study Completion
July 8, 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/.