A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
2 other identifiers
interventional
446
23 countries
205
Brief Summary
The purpose of this 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 P50-P75 for phase_3
Started Aug 2022
Typical duration for phase_3
205 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
Study Start
First participant enrolled
August 31, 2022
CompletedFirst Submitted
Initial submission to the registry
September 20, 2022
CompletedFirst Posted
Study publicly available on registry
September 23, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 17, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
September 12, 2025
CompletedOctober 22, 2025
October 1, 2025
2.3 years
September 20, 2022
October 17, 2025
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 subcutaneous (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
- Participants 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.
- Participants must be willing to comply with diet and lifestyle recommendations as able.
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 ULN 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 (205)
Central Research Associates, Inc.
Birmingham, Alabama, 35205, United States
Alabama Clinical Therapeutics, LLC Alabaster
Birmingham, Alabama, 35235, United States
Onyx Clinical Research
Peoria, Arizona, 85381, United States
NRC Research Institute
Los Angeles, California, 90015, United States
Accel Research Sites
DeLand, Florida, 32720, United States
Finlay Medical Research
Greenacres City, Florida, 33467, United States
University of Florida Jacksonville
Jacksonville, Florida, 32209, United States
Meridien Research
Maitland, Florida, 32751, United States
Columbus Clinical Services
Miami, Florida, 33125, United States
Harmony Clinical Research, Inc
North Miami Beach, Florida, 33162, United States
Combined Research Orlando Phase I-IV
Orlando, Florida, 32807, United States
3Sync Research
Sunrise, Florida, 33325, United States
R & B Medical Center LLC
Tampa, Florida, 33614, United States
JSV Clinical Research Study, Inc.
Tampa, Florida, 33634, United States
Metabolic Research Institute
West Palm Beach, Florida, 33401, United States
Emory University
Atlanta, Georgia, 30322, United States
Accel Clinical Research
Eatonton, Georgia, 31024, United States
Northeast Georgia Medical Center
Gainesville, Georgia, 30501, United States
Randomize Now
Newnan, Georgia, 30265, United States
St. Vincent Medical Group
Carmel, Indiana, 46290, United States
University of Kansas Medical Center (KUMC)
Kansas City, Kansas, 66160, United States
The Research Group of Lexington, LLC
Lexington, Kentucky, 40503, United States
University of Louisville
Louisville, Kentucky, 40202, United States
Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
Louisville, Kentucky, 40213, United States
Grace Research, LLC
Bossier City, Louisiana, 71111, United States
Clinical Trials of America LA, LLC
Monroe, Louisiana, 71201, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
Maryland Cardiovascular Specialists
Baltimore, Maryland, 21229, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Onyx Clinical Research
Flint, Michigan, 48532, United States
Onyx Clinical Research
Rochester Hills, Michigan, 48307, United States
Stern Cardiovascular
Southaven, Mississippi, 38671, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Orchard Park Family Practice
Orchard Park, New York, 14127, United States
Clinical Trials of America, LLC
Lenoir, North Carolina, 28645, United States
Diabetes and Endocrinology Consultants, P.C.
Morehead City, North Carolina, 28557, United States
OnSite Clinical Solutions, LLC
Salisbury, North Carolina, 28144, United States
The Ohio State University (OSU)
Columbus, Ohio, 43203, United States
SV Research LLC
Marion, Ohio, 43302, United States
Oklahoma Heart Institute
Tulsa, Oklahoma, 74133, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425, United States
Main Street Physicians Care Waterway
Little River, South Carolina, 29566, United States
Monument Health Clinical Research
Rapid City, South Dakota, 57701, United States
The Jackson Clinic
Jackson, Tennessee, 38305, United States
Texas Health Family Care
Fort Worth, Texas, 76107, United States
Vilo Research Group
Houston, Texas, 77017, United States
Juno Research
Houston, Texas, 77040, United States
Juno Research
Houston, Texas, 77054, United States
Clinical Trial Network
Houston, Texas, 77074, United States
Pioneer Research Solutions, Inc
Houston, Texas, 77099, United States
Sante Clinical Research, LLC
Kerrville, Texas, 78028, United States
FMC Science
Lampasas, Texas, 76550, United States
DCT - McAllen Primary Care, LLC
McAllen, Texas, 78503, United States
Texas Institute of Cardiology
McKinney, Texas, 75071, United States
SMS Clinical Research, LLC
Mesquite, Texas, 75149, United States
Southern Endocrinology Associates
Mesquite, Texas, 75149, United States
Permian Research Foundation
Odessa, Texas, 79761, United States
Diabetes & Glandular Disease Clinic, P.A.
San Antonio, Texas, 78229, United States
Tranquil Research
Webster, Texas, 77598, United States
Aspen Clinical Research
Orem, Utah, 84058, United States
Ogden Clinic Grandview
Roy, Utah, 84401, United States
Clinical Investigation Specialists Inc.
Kenosha, Wisconsin, 53144, United States
CIPREC - Centro de Investigación y Prevención Cardiovascular
Buenos Aires, C1061AAG, Argentina
Fundacion Favaloro
Buenos Aires, C1093AAS, Argentina
Centro Médico Dra. Laura Maffei
Buenos Aires, C1425AGC, Argentina
Glenny Corp SA
Buenos Aires, C1430, Argentina
Instituto de Cardiología Corrientes
Corrientes, W3400CDS, Argentina
Instituto Médico DAMIC
Córdoba, X5003DCE, Argentina
Centro Medico San Luis
San Luis, D5700, Argentina
Clínica FUSAVIM Privada
Villa María, X5900JKA, Argentina
AZ Sint-Jan Brugge
Bruges, 8000, Belgium
Hôpital Erasme
Brussels, 1070, Belgium
Virga Jessa Hospital
Hasselt, 3500, Belgium
UZ Leuven
Leuven, 3000, Belgium
NUPEC - Nucleo de Pesquisa Clinica
Belo Horizonte, 30220-140, Brazil
Núcleo de Pesquisa Clínica
Curitiba, 80730-150, Brazil
Hospital Universitario Walter Cantidio - UFC
Fortaleza, 60430-270, Brazil
Nucleo de Pesquisa em Cirurgia Vascular
Porto Alegre, 90035-903, Brazil
IBPClin Pesquisa Clinica
Rio de Janeiro, 20241-180, Brazil
CPQuali Pesquisa Clinica
São Paulo, 01228-000, Brazil
Instituto do Coração - HCFMUSP
São Paulo, 05403-000, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
São Paulo, 05403-900, Brazil
i9 Pesquisas Clínicas/Loema - Instituto de Pesquisas Clínica & Consultores
São Paulo, 13092-133, Brazil
Medical Center Diamedical EOOD
Dimitrovgrad, 6400, Bulgaria
MHAT Haskovo AD
Haskovo, 6304, Bulgaria
MHAT Pazardzhik AD
Pazardzhik, 4400, Bulgaria
UMHAT - Kaspela EOOD
Plovdiv, 4000, Bulgaria
University Multiprofile Hospital for Active Treatment Pulmed OOD
Plovdiv, 4000, Bulgaria
UMHAT Kanev AD
Rousse, 7002, Bulgaria
MHAT Sliven to MMA Sofia
Sliven, 8800, Bulgaria
Medical Center Smolyan Clinical Research OOD
Smolyan, 4700, Bulgaria
Medical Center for Specialized Medical Help in Cardiovascular Diseases OOD
Sofia, 1000, Bulgaria
Acibadem City Clinic Tokuda University Hospital
Sofia, 1407, Bulgaria
Medico Dental Center ISUL Tsaritsa Yoanna EOOD
Sofia, 1527, Bulgaria
Medical Centre Synexus Sofia EOOD
Sofia, 1784, Bulgaria
Medical Center Zara - Med
Stara Zagora, 6000, Bulgaria
DCC Equita
Varna, 9000, Bulgaria
Specialized Hospital for Active Treatment of Cardiology
Varna, 9000, Bulgaria
Medical Centre "Nevromedics" EOOD
Veliko Tarnovo, 5006, Bulgaria
NL Health Services
St. John's, Newfoundland and Labrador, A1B 3V6, Canada
Aggarwal and Associates Ltd.
Brampton, Ontario, L6T 0G1, Canada
Joanne F. Liutkus Medicine Professional Corporation
Cambridge, Ontario, N3H 4L5, Canada
Bluewater Clinical Research Group
Sarnia, Ontario, N7t 4X3, Canada
Toronto General Hospital
Toronto, Ontario, M5G2C4, Canada
Unite de Recherche Clinique
Saint-Jérôme, Quebec, J7Z 2V4, Canada
CTC Hodonin s.r.o.
Hodonín, 695 01, Czechia
KardioBusak s.r.o.
Louny, 440 01, Czechia
Fakultni nemocnice v Motole
Prague, 150 06, Czechia
Endokrinologie Cerny Most s.r.o.
Prague, 198 00, Czechia
Diabetologická a endokrinologická ambulance Milan Kvapil
Příbram, 267 01, Czechia
AeskuLab k.s
Teplice, 415 01, Czechia
Hopital de Hautepierre
Strasbourg, 67098, France
ELSAN - Polyclinique Vauban
Valenciennes, 59300, France
GHM les Portes du Sud
Vénissieux, 69200, France
University General Hospital of Alexandroupoli
Alexandroupoli, 68100, Greece
AHEPA Building of Evaggelismos
Athens, 10676, Greece
University General Hospital ATTIKON
Athens, 12462, Greece
Hygeia Hospital
Athens, 15123, Greece
AHEPA University General Hospital of Thessaloniki
Thessaloniki, 54636, Greece
Lausmed Kft.
Baja, H-6500, Hungary
DRC Gyogyszervizsgalo Kozpont Kft
Balatonfüred, H-8230, Hungary
Obudai Egeszsegugyi Centrum
Budapest, H-1036, Hungary
Clinexpert Kft.
Budapest, H1033, Hungary
Pharma4 Trial Kft.
Gyöngyös, H-3200, Hungary
Somogy Varmegyei Kaposi Mor Oktato Korhaz Diabetologiai szakrendeles
Kaposvár, H-7400, Hungary
Max Super Specialty Hospital
New Delhi, National Capital Territory of Delhi, 110017, India
B. M. Birla Heart Research Centre A Unit of the Calcutta Medical Research Institute
Kolkata, West Bengal, 700027, India
Sri Jayadeva Institute of Cardiovascular Sciences and Research
Bengaluru, 560069, India
Sir Ganga Ram Hospital
Delhi, 110060, India
Eternal Hospital
Jaipur, 302017, India
IPGMER
Kolkata, 700020, India
Vinaya Hospital and Research Centre (A Unit of Karnataka Institute of Medical Sciences)
Mangaluru, 575003, India
KEM Hospital
Mumbai, 4000012, India
Bhatia Hospital
Mumbai, 400007, India
Manipal Hospital Mysore
Mysore, 570015, India
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Bergamo, 24127, Italy
AORN S. Anna e S. Sebastiano UOC FARMACIA
Caserta, 81100, Italy
Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna
Cona, 44124, Italy
Fondazione I.R.C.C.S. Policlinico "San Matteo" c/o C.U.R.M.
Pavia, 27100, Italy
Saules seimons medicinos centras
Kaunas, 49449, Lithuania
Klinikiniai sprendimai
Kaunas, LT-49387, Lithuania
Clinic of Cardiology and Rehabilitation
Klaipėda, LT-91131, Lithuania
Republican Panevezys Hospital
Panevezys, LT-35144, Lithuania
Pirmoji viltis
Šiauliai, LT-76206, Lithuania
Sultanah Bahiyah Hospital
Alor Star, Kedah, 05460, Malaysia
Hospital Taiping
Taiping, Perak, 34000, Malaysia
Pulau Pinang Hospital
George Town, Pulau Pinang, 10450, Malaysia
University Malaya Medical Centre (UMMC)
Kuala Lumpur, 59100, Malaysia
Medical Care and Research S.A de C.V.
Mérida, Yucatán, 97070, Mexico
Centro de Investigación Cardiométabolica de Aguascalientes S.A. de C.V.
Aguascalientes, 20230, Mexico
Cientia Investigacion Clinica Sc
Chihuahua City, 32103, Mexico
Clinstile, S.A. de C.V.
Mexico City, 06700, Mexico
Clinical Research Institute S.C.
Tlanepantla, 54055, Mexico
Vumc Amsterdam Medical Center
Amsterdam, 1081BT, Netherlands
Gelre Ziekenhuizen Apeldoorn
Apeldoorn, 7334 DZ, Netherlands
Reinier de Graaf Ziekenhuis
Delft, 2625 AD, Netherlands
Het Van Weel Bethesda ziekenhuis
Dirksland, 3247BW, Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, 3318 AT, Netherlands
Bethesda Diabetes Research Center
Hoogeveen, 7909 AA, Netherlands
Canisius-Wilhelmina Ziekenhuis (CWZ)
Nijmegen, 6532 SZ, Netherlands
UCK, I Klinika Kardiologii
Gdansk, 80-214, Poland
Biokinetica
Józefów, 05-410, Poland
Centrum Medyczne Pratia
Katowice, 40-081, Poland
Centra Medyczne Medyceusz
Lodz, 91-053, Poland
Clinical Best Solutions
Lublin, 20-078, Poland
Etg Lublin
Lublin, 20-412, Poland
Centrum Zdrowia Metabolicznego
Poznan, 60-589, Poland
Clinical Best Solutions Sp. Z.o.o Spolka Komandytowa
Warsaw, 00-710, Poland
Centrum Medycnze AMED
Warsaw, 03-291, Poland
Narodowy Instytut Kardiologii im. S. Wyszyńskiego - PIB
Warsaw, 04-628, Poland
ETG Zamosc / Pro Life Medica Sp. z o.o.
Zamość, 22-400, Poland
Hospital CUF Tejo
Lisbon, 1350-352, Portugal
Centro Hospitalar de Entre Douro e Vouga
Santa Maria da Feira, 4520-211, Portugal
Cabinet Medical Individual SC DIANA BARBONTA SRL
Alba, 510053, Romania
Cardioplus Center SRL
Baia Mare, 430123, Romania
Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed S.R.L
Brasov, 500283, Romania
Centrul Medical Medicover Victoria
Bucharest, 10626, Romania
S.C. SAL MED S.R.L., Cardiologie
Piteşti, 10437, Romania
Cardio Med SRL
Târgu Mureş, 540124, Romania
S.C. Mediab Srl
Târgu Mureş, 540142, Romania
Alian s.r.o.
Bardejov, 08501, Slovakia
Ambulancia diabetologicka a poruch latkovej premeny a vyzivy
Bratislava, 83106, Slovakia
Interna a diabetologicka ambulancia - IN-DIA s.r.o.
Lučenec, 98401, Slovakia
Diab sro
Rožňava, 04801, Slovakia
Interna SK, s.r.o.
Svidník, 08901, Slovakia
Areteus s.r.o
Trebišov, 07501, Slovakia
Hospital Germans Trias i Pujol
Badalona, 8916, Spain
Hospital Vall d'Hebron
Barcelona, 8035, Spain
Hospital Comarcal Infanta Elena
Huelva, 21007, Spain
Hospital Universitario de Jaen
Jaén, 23007, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Regional de Malaga
Málaga, 29009, Spain
Unidad de Ensayos Clinicos
Málaga, 29010, Spain
Hospital Provincial de Conxo
Santiago de Compostela, 15706, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
Acardo MedSite
Solna, SE-171 64, Sweden
Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
Kaohsiung City, 80756, Taiwan
Mackay Memorial Hospital
New Taipei City, 251404, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
National Cheng Kung University Hospital
Tainan, 704017, Taiwan
Shin Kong Wu Ho-Su Memorial Hospital
Taipei, 111045, Taiwan
Chang Gung Medical Foundation - Linkou Branch
Taoyuan District, 33305, Taiwan
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
September 20, 2022
First Posted
September 23, 2022
Study Start
August 31, 2022
Primary Completion
December 17, 2024
Study Completion
September 12, 2025
Last Updated
October 22, 2025
Record last verified: 2025-10
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/.