A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia

NCT ID: NCT05079919

Last Updated: 2026-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

617 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-25

Study Completion Date

2025-07-08

Brief Summary

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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.

Detailed Description

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This is a multi-center, randomized, double-blind, placebo-controlled study in 617 participants. Participants will be randomized to receive olezarsen or placebo in a 53-week treatment period. The length of participation in the study will be approximately 78 weeks, which includes an up to 12-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period or transition to open-label extension (OLE) study with up to 1-year treatment.

Conditions

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Severe Hypertriglyceridemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Olezarsen

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.

Group Type EXPERIMENTAL

Olezarsen

Intervention Type DRUG

Olezarsen will be administered by SC injection.

Placebo

Olezarsen-matching placebo will be administered once every 4 weeks by SC injection from Week 1 through Week 49.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Olezarsen-matching placebo will be administered by SC injection.

Interventions

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Olezarsen

Olezarsen will be administered by SC injection.

Intervention Type DRUG

Placebo

Olezarsen-matching placebo will be administered by SC injection.

Intervention Type DRUG

Other Intervention Names

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AKCEA-APOCIII-LRx ISIS 678354

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Accel Research Sites Network

Birmingham, Alabama, United States

Site Status

Mayo Clinic

Scottsdale, Arizona, United States

Site Status

Velocity Clinical Research

Chula Vista, California, United States

Site Status

Diabetes/Lipid Management & Research Center

Huntington Beach, California, United States

Site Status

University of California, San Diego (UCSD)

La Jolla, California, United States

Site Status

LA Universal Research Center, Inc.

Los Angeles, California, United States

Site Status

America Clinical Trials

Tarzana, California, United States

Site Status

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, United States

Site Status

Southeast Clinical Research LLC

Chiefland, Florida, United States

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Westside Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Finlay Medical Research

Miami, Florida, United States

Site Status

Innovia Research Center, INC

Miramar, Florida, United States

Site Status

Ocala Cardiovascular Research

Ocala, Florida, United States

Site Status

IMA Clinical Research

St. Petersburg, Florida, United States

Site Status

VICIS Clinical Research

Tampa, Florida, United States

Site Status

Bayside Clinical Research

Trinity, Florida, United States

Site Status

IACT Health

Columbus, Georgia, United States

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IMA Clinical Research Chicago

Chicago, Illinois, United States

Site Status

Affinity Health

Oak Brook, Illinois, United States

Site Status

West Broadway Clinic

Council Bluffs, Iowa, United States

Site Status

Kansas University Medical Center

Kansas City, Kansas, United States

Site Status

Clinical Trials of America, LLC

Monroe, Louisiana, United States

Site Status

Continental Clinical Solutions

Towson, Maryland, United States

Site Status

University of Michigan Hospital and Health Systems/ Dept. of Pharmacy-Research Pharmacy

Ann Arbor, Michigan, United States

Site Status

Aa Mrc, Llc

Flint, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

IMA Clinical Research

St Louis, Missouri, United States

Site Status

Bryan Medical Center Clinical Research

Lincoln, Nebraska, United States

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Palm Research Center, INC.

Las Vegas, Nevada, United States

Site Status

Hudson County Clinical Trials Research Center

Union City, New Jersey, United States

Site Status

Modern Medicine

Brooklyn, New York, United States

Site Status

Northwell Health

Great Neck, New York, United States

Site Status

Circuit Clinical (Crystal Run Healthcare)

Middletown, New York, United States

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NYU Langone

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Circuit Clinical

Niagara Falls, New York, United States

Site Status

Modern Medical

Syosset, New York, United States

Site Status

Novant Health Cancer Institute Elizabeth Investigational Drug Services

Charlotte, North Carolina, United States

Site Status

Cone Medical Center

Greensboro, North Carolina, United States

Site Status

Clinical Trials of America, LLC

Mount Airy, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Salem, North Carolina, United States

Site Status

Aventiv Research

Columbus, Ohio, United States

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Summit Research Group, LLC

Munroe Falls, Ohio, United States

Site Status

Hightower Clinical Trial Services

Oklahoma City, Oklahoma, United States

Site Status

Velocity Clinical Research

Medford, Oregon, United States

Site Status

The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Health Concepts

Rapid City, South Dakota, United States

Site Status

Chattanooga Research & Medicine, PLLC

Chattanooga, Tennessee, United States

Site Status

Velocity Clinical Research

Cedar Park, Texas, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Medicus Alliance Clinical Research

Sugar Land, Texas, United States

Site Status

Velocity Clinical

West Jordan, Utah, United States

Site Status

Manassas Clinical Research Center

Manassas, Virginia, United States

Site Status

York Clinical Research LLC

Norfolk, Virginia, United States

Site Status

West Virginia University Heart and Vascular Institute

Morgantown, West Virginia, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

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Royal North Shoe Hospital

Saint Leonards, New South Wales, Australia

Site Status

Dr. Heart Pty Ltd at Cholesterol Care Australia

Woolloongabba, Queensland, Australia

Site Status

Monash Medical Centre

Clayton S., Victoria, Australia

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The Alfred Hospital

Melbourne, Victoria, Australia

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Royal Adelaide Hospital

Adelaide, , Australia

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MHAT Blagoevgrad AD

Blagoevgrad, , Bulgaria

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Medical Center Doctor Staykov EOOD

Burgas, , Bulgaria

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Medical Center Diamedical 2013 OOD

Dimitrovgrad, , Bulgaria

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MHAT "Dr. Tota Venkova" AD

Gabrovo, , Bulgaria

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Medical Center "Hera" EOOD

Montana, , Bulgaria

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SHAT "Special Medic" Ltd

Plovdiv, , Bulgaria

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Medical Center Rusemed EOOD

Rousse, , Bulgaria

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DCC 1 Sliven

Sliven, , Bulgaria

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Gabriela Zhelyazkova

Sliven, , Bulgaria

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Medical Center Smolyan Clinical Research OOD

Smolyan, , Bulgaria

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Medical Center Endomedical EOOD

Sofia, , Bulgaria

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Medical Centar "KALIMAT"

Sofia, , Bulgaria

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MC Doctor Kalchev OOD

Sofia, , Bulgaria

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UMHAT Sofiamed OOD

Sofia, , Bulgaria

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New Rehabilitation Center

Stara Zagora, , Bulgaria

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UMHAT Prof. Dr. Stoyan Kirkovich AD, Clinic of Cardiology

Stara Zagora, , Bulgaria

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Medical Centre Nevromedics EOOD

Veliko Tarnovo, , Bulgaria

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Arc Biosystems

Vancouver, British Columbia, Canada

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Canadian Phase Onward Inc

Toronto, Ontario, Canada

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Ecogene-21

Chicoutimi, Quebec, Canada

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Institut de recherches cliniques de Montréal (IRCM)

Montreal, Quebec, Canada

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Clinique des Maladies Lipidiques de Quebec Inc.

Québec, Quebec, Canada

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MEDICUS SERVICES s.r.o.

Brandýs nad Labem, , Czechia

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EDUMED s.r.o.

Hradec Králové, , Czechia

Site Status

Fakultní nemocnice Hradec Králové

Hradec Králové, , Czechia

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EDUMED s.r.o.

Náchod, , Czechia

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Fakultni nemocnice Ostrava

Ostrava, , Czechia

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Vseobecna fakultni nemocnice

Prague, , Czechia

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Lekarna Poliklinika Hurka

Prague, , Czechia

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Interni Ambulance

Uherské Hradiště, , Czechia

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Aalborg University Hospital

Aalborg, , Denmark

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Aarhus University Hospital

Aarhus, , Denmark

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Esbjerg Hospital

Esbjerg, , Denmark

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Bispebjerg Hospital

Frederiksberg, , Denmark

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Herlev Hospital

Herlev, , Denmark

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Godstrup Regional Hospital

Herning, , Denmark

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Regionshospitalet Viborg

Viborg, , Denmark

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Turku University Hospital

Turku, , Finland

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Ylitornio Health Care Center

Ylitornio, , Finland

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Hôpital Louis Pradel

Bron, , France

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CHU Dijon Bourgogne

Dijon, , France

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Hopital de la Conception

Marseille, , France

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CHU Montpellier - Hôpital Lapeyronie

Montpellier, , France

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Hopital Pitie Salpetriere APHP

Paris, , France

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CHU Nantes - Hopital Nord Laennec

Saint-Herblain, , France

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Stoffwechselcentrum Charite Campus Virchow

Berlin, , Germany

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Uniklinik Köln

Cologne, , Germany

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Universitaetsklinikum Carl Gustav Carus an der TU Dresden

Dresden, , Germany

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Klinische Forschung Hamburg GmbH

Hamburg, , Germany

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Klinische Forschung Hannover-Mitte GmbH

Hanover, , Germany

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St. Josefskrankenhaus,

Heidelberg, , Germany

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Praxis Dr. med. Taggeselle

Markkleeberg, , Germany

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Kardiologische Praxis in Papenburg

Papenburg, , Germany

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Evangelisches Krankenhaus Witten

Witten, , Germany

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BKS Research Kft

Hatvan, Heves County, Hungary

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Medifarma 98 Kft

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

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CRU Hungary Kft

Borsod, , Hungary

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Észak-Pesti Centrumkórház - Honvédkórház; II. Belgyógyászati Osztály

Budapest, , Hungary

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Semmelweis Egyetem Kardiológiai Rehabilitacio

Budapest, , Hungary

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Belinus BT

Debrecen, , Hungary

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Debreceni Egyetem Klinikai Kozpont Belgyogyaszat A epulet

Debrecen, , Hungary

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IPR Hungary Kft.

Miskolc, , Hungary

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Borbanya Praxis Eü KFT

Nyíregyháza, , Hungary

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Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, , Hungary

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DRC Gyogyszervizsgalo Kozpont Kft

Veszprém, , Hungary

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SOROKA Medical Center

Beersheba, , Israel

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Bnai Zion Medical Center

Haifa, , Israel

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Lady Davis Carmel Medical Center

Haifa, , Israel

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Shaare Zedek Medical Center

Jerusalem, , Israel

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Hadassah Hebrew University Ein Kerm MC

Jerusalem, , Israel

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Rabin Medical Center

Petah Tikva, , Israel

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Kaplan Medical Center

Rehovot, , Israel

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Sourasky Medical Center

Tel Aviv, , Israel

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Sheba Medical Center

Tel Litwinsky, , Israel

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IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico di SantOrsola

Bologna, , Italy

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Ospdale E. Bassini

Milan, , Italy

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ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

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Azienda Ospedaliera Universitaria Federico II

Napoli, , Italy

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A.O. Policlinico Universitario P. Giaccone

Palermo, , Italy

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Policlinico Umberto

Roma, , Italy

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Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Roma, , Italy

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Academic Medical Center - Department of Vascular Medicine

Amsterdam, , Netherlands

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Rijnstate Arnhem

Arnhem, , Netherlands

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Albert Schweitzer ziekenhuis

Dordrecht, , Netherlands

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Ziekenhuis Gelderse Vallei

Ede, , Netherlands

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Radboud UMC

Nijmegen, , Netherlands

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Erasmus MC

Rotterdam, , Netherlands

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Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

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Auckland City Hospital

Grafton, Auckland, New Zealand

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New Zealand Clinical Research

Christchurch, , New Zealand

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Wellington Regional Hospital

Newtown, , New Zealand

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Lipid Clinic

Oslo, , Norway

Site Status

Salvia

Katowice, , Poland

Site Status

Praktyka Lekarska Ewa Krzyzagorska

Poznan, , Poland

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ClinMedica Research Sp.z o.o.

Skierniewice, , Poland

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Osrodek Badan Klinicznych Metabolica

Tarnów, , Poland

Site Status

Futuremeds sp. z o.o

Wroclaw, , Poland

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Instytut Centrum Zdrowia Matki Polki Klinika

Łódz, , Poland

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Centro Hospitalar do Baixo Vouga Hospital Infante D. Pedro

Aveiro, , Portugal

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Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, , Portugal

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Hospital Egas Moniz - Centro Hospitalar de Lisboa Ocidental

Lisbon, , Portugal

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Centro Hospitalar Universitário de São João Consultas Externas de Endocrinologia K13

Porto, , Portugal

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Centro Hospitalar

Vila Nova de Gaia, , Portugal

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Medispektrum s.r.o., diabetologicka a metabolicka ambulancia

Bratislava, , Slovakia

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Nemocnica s poliklinikou Brezno

Brezno, , Slovakia

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Human-Care s.r.o.

Košice, , Slovakia

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Vychodoslovensky Ustav srdcovych a cievnych chorob a.s.

Košice, , Slovakia

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Cardio D&R

Košice, , Slovakia

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Nemocnica arm. generala L. Svobodu Svidnik,

Svidník, , Slovakia

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Iatros International

Bloemfontein, Free State, South Africa

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Unitas Hospital

Centurion, Gauteng, South Africa

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Dr Jan Engelbrecht and Ass. Inc

Cape Town, Western Cape, South Africa

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TREAD Research - Department of Cardiology

Parow, Western Cape, South Africa

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University of Cape town - Lipid Factory

Cape Town, , South Africa

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Chatsmed Garden Hospital

Chatsworth, , South Africa

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Hospital Abente y Lago

A Coruña, , Spain

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Hospital de la Santa Creu i de Sant Pau

Barcelona, , Spain

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Hospital Clinic Barcelona

Barcelona, , Spain

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Institut d'Investigació i Innovació Parc Taulí (I3PT) Departament Medicina Universitat

Barcelona, , Spain

Site Status

Hospital Universitari de Bellvitge

Barcelona, , Spain

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Hospital Universitario Reina Sofia

Córdoba, , Spain

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Clinica Universidad de Navarra

Madrid, , Spain

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Hospital Universitario

Madrid, , Spain

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Hospital Virgen del Rocio Edificio Centro de Diagnostico y Tratamiento (CDT)

Seville, , Spain

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Hospital Universitari Sant Joan de Reus.

Tarragona, , Spain

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Sahlgrenska, University Hospital

Gothenburg, Västra Götaland County, Sweden

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Karolinska University Hospital Huddinge

Stockholm, , Sweden

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Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Ege University School of Medicine, Department of Cardiology

Izmir, , Turkey (Türkiye)

Site Status

Kocaeli University Faculty of Medicine

Kocaeli, , Turkey (Türkiye)

Site Status

Necmettin Erbakan University Meram Medical Faculty

Konya, , Turkey (Türkiye)

Site Status

Oak Tree Surgery and Pensilva Health Centre

Liskeard, Cornwall, United Kingdom

Site Status

Newquay Health Centre

Newquay, Cornwall, United Kingdom

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Upton Surgery

Poole, Dorset, United Kingdom

Site Status

Panthera Biopartners

Rochdale, England, United Kingdom

Site Status

Panthera Biopartners

Sheffield, England, United Kingdom

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Huddersfield Royal Infirmary

Lindley, Huddersfield, United Kingdom

Site Status

Lakeside Healthcare at Corby

Corby, Northamptonshire, United Kingdom

Site Status

Sandwell General Hospital

Lyne, West Bromwich, United Kingdom

Site Status

Waterloo Medical Centre

Blackpool, , United Kingdom

Site Status

Mounts Bay Medical Hub

Cornwell, , United Kingdom

Site Status

Panthera

Glasgow, , United Kingdom

Site Status

Hull Royal Infirmary

Hull, , United Kingdom

Site Status

Panthera

London, , United Kingdom

Site Status

Manchester University NHS Foundation Trust (MFT)

Manchester, , United Kingdom

Site Status

Panthera

Preston, , United Kingdom

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Primary Care Sheffield

Sheffield, , United Kingdom

Site Status

Countries

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United States Australia Bulgaria Canada Czechia Denmark Finland France Germany Hungary Israel Italy Netherlands New Zealand Norway Poland Portugal Slovakia South Africa Spain Sweden Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 41211918 (View on PubMed)

Marston 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.

Reference Type DERIVED
PMID: 40064331 (View on PubMed)

Other Identifiers

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2021-002192-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-510696-38-00

Identifier Type: CTIS

Identifier Source: secondary_id

ISIS 678354-CS5

Identifier Type: -

Identifier Source: org_study_id

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